CN110384720A - A kind of hippophae rhamnoides compositions and its preparation method and application - Google Patents

A kind of hippophae rhamnoides compositions and its preparation method and application Download PDF

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CN110384720A
CN110384720A CN201810343377.5A CN201810343377A CN110384720A CN 110384720 A CN110384720 A CN 110384720A CN 201810343377 A CN201810343377 A CN 201810343377A CN 110384720 A CN110384720 A CN 110384720A
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hippophae
hippophae rhamnoides
auxiliary material
leaves
preparation
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张志锋
吕露阳
刘璇
薛樵
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Southwest Minzu University
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
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    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605Excipients; Inactive ingredients
    • A61K9/1617Organic compounds, e.g. phospholipids, fats
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    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
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    • A61K2236/50Methods involving additional extraction steps
    • A61K2236/51Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying

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Abstract

The invention belongs to the field of Chinese medicines, and in particular to a kind of hippophae rhamnoides compositions, including hippophae rhamnoides and auxiliary material, the auxiliary material are alpha-lactose, mannitol or soluble starch.The present invention is made hippophae rhamnoides compositions particle and has excellent stability, and hydroscopicity is low.

Description

A kind of hippophae rhamnoides compositions and its preparation method and application
Technical field
The present invention relates to a kind of hippophae rhamnoides compositions and its preparation method and application.
Background technique
Sea-buckthorn also known as arrow-leaved oleaster, fructus hippophae, black thorn, acid thorn;Fruit shapes are subsphaeroidal or oval, and sea-buckthorn distribution is extremely wide, It is all distributed in the temperate zone of two hemispheres to the torrid zone;Northwest, North China, each provinces and regions in southwest in China are also distributed, and China possesses the world Upper the most abundant sea buckthorn resources.In fructus hippophae in addition to containing protein, fat, carbohydrate, there are also a variety of necessary to human body Vitamin and inorganic salts, wherein vitamin content is abundant, including VB1, VB2, VB6 (folic acid), VC, VE, VK (phylloquinone), VP and Carotenoid etc.;Especially it is height with VC content, almost occupies the hat of all fruits and vegetables, it may be up to 800 containing VC in every hectogram fructus hippophae~ 1907mg reaches as high as 2100mg or more.In addition, Hippophae (rhamnoides) original juice also contains VK1, VA, VB1, VB2, it is husky in all berries Vitamin content highest in spine, therefore have the title of " vitamin treasure-house ".Sea-buckthorn citrin powder is catechin, white anthocyanidin, cyanine The general designation of element, flavones, flavonols, chalcone, deoxidation chalcone, fragrant glycosides and phenolic acid.Sea-buckthorn citrin powder used in the present invention Middle Vc content is up to 5000mg/L, additionally has strengthen immunity, improves growth and development function, improves anoxia endurance function Can, reducing blood lipid, function of blood sugar reduction are assisted, lead-expelling function etc. is promoted.It is mainly used for health food, functional food ingredient, common Raw-food material, pharmaceutical raw material etc..
It is applied for many years through clinical, sea-buckthorn particle is curative for effect to illnesss such as relieving cough and reducing sputum, chronic bronchitis, sea-buckthorn particle System uses the auxiliary materials such as hippophae rhamnoides and sucrose, microcrystalline cellulose, gelatin, glycerol, vegetable oil, magnesium stearate, ethyl cellulose Compatibility is made.But this sea-buckthorn particle still has that hygroscopicity is strong, and particle is unstable, the low problem of ratio of briquetting.
Application No. is a kind of cough-relieving apophlegmatic of 200810046037.2 patent application, relieving dyspepsia, promoting blood circulation to remove blood stasis drug And preparation method thereof, it discloses using solid content rhamnoides extract, mannitol, dextrin, soluble starch, Steviosin preparation sea-buckthorn class Drug, it is big that there are supplementary product consumptions, at high cost, the problem of preparation process complexity.
Summary of the invention
The present invention in order to solve the problems existing in the prior art, provides a kind of hippophae rhamnoides compositions and its preparation method and application.
Hippophae rhamnoides compositions are mainly prepared by hippophae rhamnoides and pharmaceutically acceptable auxiliary material.
Applicants have found that supplementary product kind and dosage have apparent shadow to the stability and ratio of briquetting of hippophae rhamnoides compositions It rings, the excessive hygroscopicity enhancing that will cause hippophae rhamnoides compositions of supplementary product consumption causes stability to decline, supplementary product kind will affect sand more The mouthfeel of spine particle.
For applicant by experimental study, the auxiliary material that the hippophae rhamnoides compositions are selected is selected from alpha-lactose, mannitol or solubility Starch, finished product all have excellent stability, and hydroscopicity is low, and small on the influence of finished product mouthfeel, remain Leaves of Hippophae L Original taste.
In present invention experiment, when auxiliary material is selected from mannitol, the ratio of briquetting highest of finished product, and hydroscopicity is minimum.
In present invention experiment, when the mass ratio of the hippophae rhamnoides and auxiliary material is 1:1-2, be conducive to improve product at Type rate.Preferably, the mass ratio of the hippophae rhamnoides and auxiliary material is 1:2.
Hippophae rhamnoides of the present invention uses the method including the following contents to be prepared: Leaves of Hippophae L is crushed into powder, Extracting in water at least 1 time, filtering and merging gained filtrate is sea-buckthorn extracting solution, and sea-buckthorn extracting solution is concentrated, drying crushes Obtain hippophae rhamnoides.Further, the solid-liquid ratio 1:6-16 of the Leaves of Hippophae L and water, when single-trial extraction a length of 1-4h, extract Number is 3-4 times.In the embodiment of the present invention, the solid-liquid ratio of the Leaves of Hippophae L and water is selected from 1:12, and single-trial extraction duration is selected from 1h, Extraction time is selected from 3 times.It should be known that gained filtrate is directly entered subsequent handling operation, no conjunction when extraction time is 1 time And treatment process.
Further, the relative density of obtained medicinal extract is 1.29-1.33g/ml after the sea-buckthorn extracting solution is concentrated;Institute Stating drying temperature is 70 DEG C.
The hippophae rhamnoides compositions are used to prepare the purposes of health care product or food additives.Above-mentioned health care product or food addition Agent, also containing the different available auxiliary materials or carrier using dosage form of adaptation.Health care product is tablet, capsule or oral solution.
The present invention also provides a kind of preparation methods of hippophae rhamnoides compositions, take hippophae rhamnoides, auxiliary material, and adhesive is added, Through granulation, drying, whole grain to obtain the final product.
In present invention experiment, former, the auxiliary material quality summation and adhesive volume ratio are 6-10:1wt:vol.Preferred mass When volume ratio is 6:1, obtained hippophae rhamnoides compositions ratio of briquetting highest, hydroscopicity is minimum, stability is best.
In present invention experiment, adhesive is selected from the ethyl alcohol that mass concentration is 70-90%.Adhesive is selected from mass concentration When 90% ethyl alcohol, the ratio of briquetting highest of hippophae rhamnoides compositions.
The invention has the advantages that:
One, the hydroscopicity of the obtained hippophae rhamnoides compositions particle of the present invention is low, improves granule stability, guarantees curative effect, uses The combination of extract dry powder and auxiliary material can effectively reduce the dosage of auxiliary material compared to the combination for directlying adopt medicinal extract and auxiliary material, save Cost.
Two, single auxiliary material is selected, it is more simple and efficient in the preparation, compared to multiple auxiliary materials, the dose of single auxiliary material It reduces, but effect is identical, reduces the loss that supplementary product kind excessively causes Leaves of Hippophae L original flavor, as far as possible reservation Leaves of Hippophae L itself Taste, especially when auxiliary material be selected from mannitol when, also have certain flavoring effect, sea-buckthorn folic acid can be alleviated in a certain range Puckery mouthfeel, more preferably to user's experience sense.
Three, the present invention selects ethyl alcohol as adhesive, and grain forming can be made good, and property is stablized, compared to water As adhesive, the generation of agglomeration and the excessive situation that can not be sieved of viscosity is effectively prevented.
Four, the obtained hippophae rhamnoides compositions particle of the present invention, packing dosage is small, and taking dose is few, is suitble to crowd wide, especially just It is applied in children, is also convenient for carrying.
Five, the present invention can be used for health care product, food additives, be widely used.
Detailed description of the invention
Fig. 1 is that 3 batch Leaves of Hippophae L particle pictorial diagrams are made;
Fig. 2 is Particles at Critical relative humidity figure;
Fig. 3 is granule production technological process.
Specific embodiment
Below by specific embodiment, the present invention is described in further detail, and following embodiment can make this profession The present invention, but do not limit the invention in any way is more completely understood in technical staff.
One, instrument and material
1.1 instrument
HH-2 digital display thermostat water bath (Guo Hua Electrical Appliances Co., Ltd);METTLERAE240 electronic analytical balance;KQ-250B Type ultrasonic cleaner (Kunshan ultrasonic instrument Co., Ltd);IKARV10 type Rotary Evaporators (the Chinese mugwort limited public affairs of card instrument and equipment Department);Waters AcquityH-Class Ultra Performance Liquid Chromatography instrument (Waters, US).
1.2 materials and reagent
Chromatography methanol (Fischer company), chromatography phosphoric acid (Tianjin Kermel Chemical Reagent Co., Ltd.);Ultrapure water. Quercetin (lot number: 16022301, Chengdu Kang Bang Biotechnology Co., Ltd), Kaempferol (lot number: 15120415, Chengdu health nation Biotechnology Co., Ltd), Isorhamnetin (lot number: 15100348, Chengdu Kang Bang Biotechnology Co., Ltd), purity >= 98%.Food-grade alpha-lactose, soluble starch, dextrin, mannitol, xylitol, glucose (the limited public affairs of Zhengzhou Zhuo Yan biotechnology Department).
Two, method and result
The selection of 2.1 dosage forms
Larger, the piece in conjunction with Leaves of Hippophae L pharmacological effect, reactive compound physicochemical property and holding conditions and decoction dose The preservative toxicity of tabletting, coating and the mixture of agent and oral solution, corrigent prepare the unfavorable factors such as complexity, and granule phase The advantages that few to supplementary product consumption, easy to process, convenient for storage carrying, therefore dosage form is determined as granule.
2.2 extraction process routes are drafted
The extracted obtained Leaves of Hippophae L Aqueous extracts of Leaves of Hippophae L are concentrated under reduced pressure, are dried to obtain extract powder, are added auxiliary material obtained Grain, then got product through whole grain, packing.
2.3 Study on extraction
Chinese medicine extraction process ensures the important link of resource utilization He the effective drug effect of its preparation safety, early-stage study table It is highly polar flavone compound in aglycon that main active, which is Quercetin, Kaempferol, Isorhamnetin etc., in bright Leaves of Hippophae L, Therefore this granule raw material is extracted using the stronger pure water of polarity, is to refer mainly to Quercetin, Kaempferol, Isorhamnetin content Mark, and using paste-forming rate as auxiliary characteristics, determine optimum extraction process.
2.3.1 single factor exploration
The influence of solid-liquid ratio: precision weighs 3 parts of Leaves of Hippophae L powder respectively, and every part of 5g is set in round-bottomed flask, presses feed liquid respectively Add pure water than 1:6,1:8,1:10,1:12,1:16, extracts 1h, filtering, merging filtrate is spin-dried for, using superelevation liquid chromatography Quercetin, Kaempferol, Isorhamnetin content are measured, and paste-forming rate is calculated according to the following formula.It the results are shown in Table 1.
Paste-forming rate (%)=dry cream quality/quality of medicinal material × 100%
1 solid-liquid ratio of table is investigated
Table 1 Investigation of the ratio of material to liquid
As can be seen from the results, generally with the increase of amount of water, Quercetin, Kaempferol, the content of Isorhamnetin and cream out Rate is consequently increased, and the content of especially Isorhamnetin significantly improves, based on the factors such as convenient degree and cost of extraction, using feed liquid It is extracted than 1:12.
The investigation of extraction time: precision weighs 4 parts of Leaves of Hippophae L powder respectively, and every part of 5g is set in round-bottomed flask, and 60mL is added Water extracts 1h, 2h, 3h, 4h respectively, and filtering, merging filtrate is spin-dried for, using superelevation liquid chromatography for measuring Quercetin, kaempferia galamga Phenol, Isorhamnetin content simultaneously calculate paste-forming rate.It the results are shown in Table 2.
2 extraction time of table is investigated
Table2 Investigation of the extraction time
As can be seen from the results, with the increase of extraction time, Quercetin, the content of Isorhamnetin and paste-forming rate also increase, but Increase is not obvious, to prevent the extraction time too long active constituent that may be destroyed in Leaves of Hippophae L and saving the factors such as time, Use extraction time for 1h.
The investigation of extraction time: precision weighs 4 parts of Leaves of Hippophae L powder respectively, and every part of 5g is set in round-bottomed flask, and 60mL is added Water extracts 1 time, 2 times, 3 times, 4 times respectively, and each 1h, filtering, merging filtrate is spin-dried for, using superelevation liquid chromatography for measuring Mongolian oak Pi Su, Kaempferol, Isorhamnetin content simultaneously calculate paste-forming rate.It the results are shown in Table 3.
3 extraction time of table is investigated
Table 3 Investigation of the times of extraction times
As can be seen from the results, with the increase of extraction time, Quercetin, Kaempferol, the content of Isorhamnetin and paste-forming rate Increase therewith, Isorhamnetin content increase is especially significant, and in the 3rd extraction, the content and paste-forming rate of three compounds are basic Reach saturation, increase trend tends to be steady, therefore uses 3 decoctions.
Wherein, the chromatographic condition of superelevation liquid chromatography are as follows: chromatographic column ACQUITYHSS C18(2.1mm × 100mm, 1.8 μm);Mobile phase is methanol (A) -0.2% phosphoric acid water (B), elution program are as follows: 0-3min, 5%-10%A;3- 7min, 10%-25%A;7-13min, 25%-48%A;13-17min, 48%-51%A;17-32min, 51%A-51%A; 30 DEG C of column temperature;0.15 mLmin of flow velocity-1;Sample volume: 3 μ L;Detection wavelength 370nm.
Above-mentioned superelevation liquid phase chromatogram condition is through methodological study, measurement result accurate and effective.
2.3.2 orthogonal experiment
In Leaves of Hippophae L flavone compound Quercetin, Kaempferol, the content of Isorhamnetin and paste-forming rate by solid-liquid ratio, decoct The influence of many factors such as time and extraction time is boiled, therefore, using Orthogonal Decomposition contrived experiment, to quercitrin in influence Leaves of Hippophae L Element, Kaempferol, Isorhamnetin content and paste-forming rate factor investigated comprehensively.
Quadrature factor level design: 4 are shown in Table, Orthogonal Experiment and Design and result, correlation analysis are shown in Table 5,6,7,8,9.
4 factor level table of table
Table 4 Level of factors
5 Orthogonal experiment results table of table
Table 5 The results oforthogonal experimental
6 paste-forming rate variance interpretation of result of table
Table 6 Analysis ofvariance results ofointment rate
7 quercetin content variance analysis of results table of table
Table 7 Analysis ofvariance results ofquercetin content
8 kaempferia galamga phenol content variance interpretation of result of table
Table 8 Analysis ofvariance results ofkaempferol content
9 Isorhamnetin content variance interpretation of result of table
Table 9 Analysis ofvariance results ofISO rhamnolipid content
Interpretation of result: according to orthogonal experiment and variance interpretation of result it is found that paste-forming rate degree of susceptibility is followed successively by extraction time (C) > solid-liquid ratio (A) > extraction time (B), optimal combination A2B3C3;In quercetin content measurement, influence degree is followed successively by Extraction time (C) > extraction time (B) > solid-liquid ratio (A), optimal combination A3B1C3;In Kaempferol assay, extract secondary Number (C) > solid-liquid ratio (A) > extraction time (B), optimal combination A1B2C3;In Isorhamnetin assay, influence degree according to Secondary is extraction time (C) > extraction time (B) > solid-liquid ratio (A), optimal combination A3B1C3.It can by above-mentioned analysis result Know, three solid-liquid ratio (A), extraction time (B), extraction time (C) factor differences are not significant, since extraction time (C) is at 3 It plays main influence in inspection target, therefore extraction time is determined as 3 times, in conjunction with single factor exploration experimental result, really Determine optimum extraction process are as follows: A3B1C3, i.e. solid-liquid ratio be 1:12, extraction time 1h, extraction time 3 times.
2.3.3 verification test
Precision weighs 3 parts of Leaves of Hippophae L powder, every part of 100g, according to optimal conditions parallel extraction 3 times of above-mentioned determination, to out Cream rate, Quercetin, Kaempferol, Isorhamnetin content are measured, the results showed that the extraction process is stablized feasible.
10 verification test result of table
Table 10 The results of verification experiment
2.4 concentrations and drying process research
2.4.1 concentration technology is investigated
In pelletization, the medicinal extract obtained after medicinal material extract concentration is one of the key technology for determining preparation process, generally Using the relative density of medicinal extract as evaluation index, relative density is bigger, and medicinal extract is more sticky, and required auxiliary material is fewer when granulation, conversely, Relative density is smaller, and medicinal extract is thinner, and mobility is stronger, and required auxiliary material is more, therefore, by measuring relative density, investigates husky The concentrating degree of spine leaf medicinal extract, determines best concentration technology.Take the sea-buckthorn leaf extract under " 2.3.3 " item in " verification test " 100,200,300,350,400mL were compared in version " Chinese Pharmacopoeia " the 4th (general rule 0601) relative density determination method by 2015 Weight bottle method (2) method is measured, and the results are shown in Table 11.
The relative density of test sample=test sample weight/water weight
11 concentration technology of table investigates result table
Table 11 Table of results of concentration process
By investigation result it is found that being 1.29-1.33g.mL when sea-buckthorn leaf extract is concentrated into relative density-1Medicinal extract when, Concentrating degree is suitable for that medicinal extract is viscous pasty state, is easy to topple over and without wall built-up phenomenon.
2.4.2 drying process is investigated
Binding experiment room relevant device condition, using traditional oven drying method as the drying mode of Leaves of Hippophae L medicinal extract, and is investigated out Cream rate and Quercetin, Kaempferol, Isorhamnetin content, further verify technology stability.By the Leaves of Hippophae L under " 2.3.3 " item It is 1.29-1.33g.mL that extracting solution normal pressure, which is concentrated into relative density,-1Medicinal extract, weigh 3 parts of medicinal extract, every part of about 30g is dried in 70 DEG C It dries in case to constant weight, sets accurately weighed after cooling in drying basin, calculating paste-forming rate, dry cream is finely ground, No. 3 sieves are crossed, fine powder is taken 0.5g measures Quercetin, Kaempferol, Isorhamnetin content by chromatographic condition under " 2.3.1 " item, the results are shown in Table 12.
12 drying process of table investigates result table
Table 12 Table of results of drying process
Paste-forming rate, quercitrin by investigation result it is found that using oven drying method when being dried for 70 DEG C, to Leaves of Hippophae L medicinal extract Element, Kaempferol, Isorhamnetin content have no significant effect, and illustrate that the drying mode is effective and feasible.
2.5 Study on Forming
2.5.1 the preparation of extract powder
The dry blade powder 12kg of sea-buckthorn is taken, is decocted with water, by solid-liquid ratio 1:12 (ml:g) plus pure water, decoction 3 times, often Secondary 1h, filtering, merging filtrate are simultaneously concentrated into relative density as 1.29-1.33g.mL-1Thick medicinal extract, dried in 70 DEG C of baking ovens, Leaves of Hippophae L dry cream is obtained, is crushed, crosses No. 3 sieves to get Leaves of Hippophae L extract powder.
2.5.2 the initial option of auxiliary material
It is auxiliary to soluble starch, alpha-lactose, mannitol, dextrin, xylitol, glucose etc. using hydroscopicity as inspection target Material carries out initial option.The glass desicator that bottom is filled NaCl supersaturated solution makes it in placing 48h in 25 DEG C of baking ovens Internal relative humidity (RH) is 75%.Each auxiliary material about 1g is weighed respectively, is respectively put into and has been dried into the weighing bottle of constant weight, gently Shaking makes it be evenly distributed, and spreading out to thickness is about 2mm, and after accurately weighed, it is dry for 75% glass to be put into internal relative humidity (RH) In dry device, bottle cap is opened, is placed in 25 DEG C of baking ovens, is weighed respectively in 2,4,8,12,24,48h], by formula: hydroscopicity % =(medicinal powder quality-moisture absorption prodrug silty amount after moisture absorption)/moisture absorption prodrug silty amount × 100% calculates hydroscopicity, the results are shown in Table 13。
Hydroscopicity of each auxiliary material of table 13 in the environment of RH75%
Table 13 The moisture absorption rate of the excipients in the Environment of RH 75%
From the data in the table, the hydroscopicity of xylitol is apparently higher than other auxiliary materials, be unfavorable for granule stability and It saves, and expensive;Glucose hydroscopicity is higher, and contains higher sugar, is unfavorable for the patients' such as diabetes, hypertension It takes.Comprehensively consider, tentatively selected alpha-lactose, mannitol and dextrin, soluble starch carry out preliminary experiment as auxiliary material.
2.5.3 auxiliary material preliminary experiment
20g Leaves of Hippophae L extract powder is taken, by extract powder: auxiliary material (1:2) forms sediment with alpha-lactose, mannitol, dextrin, solubility respectively Powder mixing is crossed No. 3 sieves and is uniformly mixed, and using 80% ethyl alcohol as adhesive softwood, crosses No. 1 sieve granulation, particle is done at 70 DEG C Dry and whole grain selects best auxiliary material using the hygroscopicity of particle, mouldability, angle of repose and dissolubility as inspection target, carries out next Orthogonal test is walked, determines the best preparation process of Leaves of Hippophae L granule.
The measurement of particle hydroscopicity: the glass desicator that bottom fills NaCl supersaturated solution is placed in 25 DEG C of baking ovens 48h, the relative humidity (RH) for keeping it internal is 75%.About 1g particle obtained above is weighed, is respectively put into and has dried to constant weight Weighing bottle in, jog makes it be evenly distributed, and thickness is about 2mm, be put into after accurately weighed internal relative humidity (RH) be 75% In glass desicator, bottle cap is opened and is taken out after 25 DEG C of baking ovens place 48h, accurately weighed, by formula: hydroscopicity %=(inhales Medicinal powder quality-moisture absorption prodrug silty amount after wet)/moisture absorption prodrug silty amount × 100%, particle hydroscopicity is calculated, the results are shown in Table 14。
Grain forming rate measurement: take particle 30g obtained above respectively, according to 2015 version " Chinese Pharmacopoeia " to granule Granularity requirements, respectively by No. 1 sieve and No. 5 sieves, wherein the summation that cannot be sieved and can be sieved by No. 5 by No. 1 is no more than 15%.By formula: ratio of briquetting %=can pass through No. 1 sieve and particle weight/particle total weight × 100% that cannot be sieved by No. 5, meter Ratio of briquetting is calculated, the results are shown in Table 14.
Fluidity determining: it using angle of repose (α) as the evaluation index of mobility of particle, is surveyed using fixed funnel method It is fixed, a graph paper is placed in the horizontal plane, and 3 funnel series connection are fixed on iron stand, make funnel bottom end away from graph paper height Spending (h) is 1cm, and particle obtained above is fallen down along top funnel wall, until hopper base termination contacts the particle on graph paper Until cone tips, cone bottom radius (r) is measured using graph paper, angle of repose is calculated, the results are shown in Table 14.Angle of repose: Tan α=h/r
Melting measurement: according to 2015 version " Chinese Pharmacopoeia " take test sample 10g, heat water 200ml, stir 5min, stand Observation is carved, particle should all dissolve or slight turbid, the results are shown in Table 14.
14 particle hydroscopicity of table, ratio of briquetting, melting investigate result table
Table 14 Investigation results ofmoistureabsorption,molding rate and solubility of particles
As preliminary experiment it is found that using dextrin as particle made from auxiliary material, hydroscopicity is higher than other auxiliary materials, and ratio of briquetting only has 10.05%, and have that apparent caking phenomenon, viscosity is big, is difficult to granulation of being sieved, therefore mobility and melting can not be investigated;α-cream Sugar, mannitol and soluble starch are particle made from auxiliary material, and hydroscopicity, ratio of briquetting and melting meet States Pharmacopoeia specifications, and Angle of repose illustrates that particle has good mobility less than 40 °, in summary as a result, selection alpha-lactose, soluble starch and sweet dew Alcohol carries out orthogonal test as auxiliary material, preferably best preparation process out.
2.5.4 orthogonal test preferred formulation technique
Experimental design: using grain forming rate as index, supplementary product kind (A), supplementary material ratio (B), concentration of alcohol are investigated (C), influence of 4 factors of ethanol consumption (D) to grain forming rate, wherein ethanol consumption (D) with former, auxiliary material quality summation with Ethyl alcohol volume ratio indicates, chooses L9(34) orthogonal table contrived experiment, preferably best preparation process out.Quadrature factor level design It is shown in Table 15.
15 factor level of table
Table 15 The level of factors
Orthogonal Experiment and Design and result: 16 are shown in Table, variance analysis is shown in Table 17.
16 Orthogonal experiment results of table
Table 16 The results of orthogonal experimental
17 the results of analysis of variance of table
Table 17 The results ofvariance analysis
As can be seen from the results, when auxiliary material is mannitol, the ratio of briquetting of particle is higher than other auxiliary materials, the influence degree of each factor It is followed successively by supplementary product kind (A) > supplementary material ratio (B) > concentration of alcohol (C) > ethanol consumption (D), since ethanol consumption is to particle The influence of ratio of briquetting is minimum, therefore carries out variance analysis as error, the results showed that, the type and supplementary material ratio of auxiliary material Significant difference between each level.In conclusion determining that the best preparation process of Leaves of Hippophae L particle is A1B3C3D3, i.e., with mannitol For auxiliary material, dosage is 2 times of raw material, using 90% ethyl alcohol as adhesive, the mass body of raw material and auxiliary material quality summation and ethyl alcohol Product is than being 6:1.
Applicant is also raw material to the medicinal extract directlyed adopt after being concentrated, and auxiliary material is added and prepares hippophae rhamnoides compositions particle, former, auxiliary Material ratio is 1:5.The application is easier to save using Leaves of Hippophae L extract powder as raw material compared to rhamnoides extract one side raw material, storage Time extension is deposited, property is more stable, on the other hand can reduce the dosage of auxiliary material, and former, auxiliary material proportion 1:2 can be reduced into This.
2.5.5 verification test
Extract powder 30g obtained under " 2.5.1 " item is taken, is made in parallel by the optimum process condition A1B3C3D3 of above-mentioned determination 3 batches of Leaves of Hippophae L particles are obtained, the ratio of briquetting for measuring particle is respectively 95.67%, 94.91%, 96.18%, RSD 0.67%, table The bright stable preparation process is reliable.
2.5.6 the measurement of Particles at Critical relative humidity (CRH)
The hygroscopicity of drug has a major impact the quality and stability of preparation.Moisture absorption is the characteristic of solid pharmaceutical preparation, is faced Boundary's relative humidity (CRH) is the hygroscopic index value of drug, and CRH value is smaller, shows that drug hygroscopicity is stronger, otherwise CRH bigger, Drug is less susceptible to moisture absorption.There are many hydrophilic compositions, easily moisture absorption in Chinese materia medica preparation, therefore measure CRH size, evaluates accordingly The size of relative humidity (RH) provides reference in the production process of Chinese materia medica preparation.
Using the CRH of powder moisture absorption method measurement Leaves of Hippophae L particle, by various concentration H2SO4With the satiety of various concentration NaCl It is placed on glass desicator bottom with solution, places 48h in 25 DEG C of baking oven, drier internal relative humidity is made to reach flat Weighing apparatus, takes in " 2.5.5 " 14 parts of Leaves of Hippophae L particle prepared under " verification test " item, and every part of about 1g is placed in dry to constant weight Weighing bottle in, two parts are put in each drier, jog makes it be evenly distributed, and spreading out to thickness is about 2mm, accurately weighed, beats Weigh the cap is opened, places 48h in 25 DEG C of baking ovens, it is accurately weighed after taking-up, calculate the suction of Leaves of Hippophae L particle under various circumstances Wet rate, the results are shown in Table 18.Moisture percentage (%) with particle is ordinate, relative humidity (RH) is that abscissa draws curve, The critical relative moisture (CRH) that particle is determined by the abscissa of the curve both ends point of intersection of tangents, is as a result shown in Fig. 2.
18 particle hydroscopicity of table and various concentration sulfuric acid and salt relative humidity investigation table
Table 18 Investigation of the moisture absorption rate and the relative humidity of sulphuric acid and salt with different concentrations
As seen from the figure, 25 DEG C when, the critical humidity of Leaves of Hippophae L particle is 70%, is illustrated under this condition, the physics of particle Property is stablized, and therefore, during preparing particle, should control wettability 70% hereinafter, storage and storage in favor of particle, Guarantee the stability of particle.
The determination of 2.6 Leaves of Hippophae L particle sizes
Referring in 2015 version " Chinese Pharmacopoeia " also based on the derivative of the aglycons such as Quercetin, Kaempferol and Isorhamnetin Related specification under " capsule of ginkgo leaves " item of active material is wanted, " capsule of ginkgo leaves " determines Quercetin, Kaempferol and different sandlwood Cellulose content, and according to formula: total flavonoids content=(quercetin content+kaempferia galamga phenol content+Isorhamnetin content) × 2.51, General flavone glycoside content is converted into as assay index, it is specified that every content containing general flavone glycoside must not less than 19.2mg, 3 times a day, 1-2 each.This experiment is as referring to foundation.By " verification test " in " 2.3.3 " it is found that pressing best work The Leaves of Hippophae L that skill the is extracted paste-forming rate that be averaged is 20.72%, Quercetin in the Leaves of Hippophae L of Unit Weight, Kaempferol, Isorhamnetin Average content is respectively 1.33mg.g-1、0.43mg.g-1、6.67mg.g-1, Quercetin, Kaempferol and Isorhamnetin it is average total Content is 8.4mg.g-1, being scaled total flavonoids content is 21.2 mg.g-1, therefore, the specification of Leaves of Hippophae L particle is set to 1.5g/ bags, 2 times a day.
2.7 process flow chart
Detailed process is detailed in attached drawing 3.
2.8 prescription small-scale experiments
By above-mentioned optimum extraction process and preparation process, Leaves of Hippophae L particle is prepared, prepares 3 batches of samples, every batch of in parallel 1000g carries out small-scale experiment, 3 batches of sample datas of gained and run-of-the-mill inspection result, is shown in Table 19 and 20.
193 batches of sample experimental results of table
Table 19 Experimental results of 3 samples
20 3 batches of sample survey results of table
Table 20 Test results of 3 samples
In order to further verify the stability of Leaves of Hippophae L granule formation technology, it is small to have carried out prescription for Binding experiment room condition It has a try and tests, the results showed that, 3 batches of laboratory sample parameters are consistent, meet requirements under " Chinese Pharmacopoeia " granule item, Illustrate that the process stabilizing is feasible, can in high volume put into production.
The above description is merely a specific embodiment, but scope of protection of the present invention is not limited thereto, any Those skilled in the art within the technical scope disclosed by the invention, can without the variation that creative work is expected or Replacement, should be covered by the protection scope of the present invention.Therefore, protection scope of the present invention should be limited with claims Subject to fixed protection scope.

Claims (10)

1. a kind of hippophae rhamnoides compositions, it is characterised in that: including hippophae rhamnoides and auxiliary material, the auxiliary material is alpha-lactose, mannitol Or soluble starch.
2. hippophae rhamnoides compositions according to claim 1, it is characterised in that: the auxiliary material is selected from mannitol.
3. hippophae rhamnoides compositions according to claim 1, it is characterised in that: the mass ratio of the hippophae rhamnoides and auxiliary material is 1: 1-2;Preferably 1:2.
4. hippophae rhamnoides compositions according to claim 1, which is characterized in that the preparation method of the hippophae rhamnoides, including with Lower content: Leaves of Hippophae L is crushed into powder, and extracting in water at least 1 time, filtering and merging gained filtrate is sea-buckthorn extracting solution, will be husky Spine extracting solution is concentrated, dry, crushing obtains hippophae rhamnoides.
5. hippophae rhamnoides compositions according to claim 4, it is characterised in that: the solid-liquid ratio 1:6-16 of the Leaves of Hippophae L and water, it is single A length of 1-4h when secondary extraction, extraction time are 3-4 times;Preferably, the solid-liquid ratio of the Leaves of Hippophae L and water is selected from 1:12, and single mentions Duration is taken to be selected from 1h, extraction time is selected from 3 times.
6. hippophae rhamnoides compositions according to claim 4, it is characterised in that: obtained medicinal extract after the sea-buckthorn extracting solution is concentrated Relative density is 1.29-1.33g/ml;The drying temperature is 70 DEG C.
7. the purposes that any hippophae rhamnoides compositions of claim 1-6 are used to prepare health care product or food additives.
8. a kind of preparation method of hippophae rhamnoides compositions, it is characterised in that: take hippophae rhamnoides, auxiliary material, adhesive is added, through making Grain, dry, whole grain to obtain the final product.
9. the preparation method of hippophae rhamnoides compositions according to claim 8, it is characterised in that: the raw material and auxiliary material summation and viscous Mixture mass volume ratio (wt:vol) is 6-10:1.
10. the preparation method of hippophae rhamnoides compositions according to claim 8, it is characterised in that: described adhesive is mass concentration For the ethyl alcohol of 70-90%;The ethyl alcohol that preferred mass concentration is 90%.
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Application publication date: 20191029