CN104524000A - Eyesight-improving fast release drop pills capable of rapidly improving visual fatigue and preparation method thereof - Google Patents

Eyesight-improving fast release drop pills capable of rapidly improving visual fatigue and preparation method thereof Download PDF

Info

Publication number
CN104524000A
CN104524000A CN201510030471.1A CN201510030471A CN104524000A CN 104524000 A CN104524000 A CN 104524000A CN 201510030471 A CN201510030471 A CN 201510030471A CN 104524000 A CN104524000 A CN 104524000A
Authority
CN
China
Prior art keywords
volume
dry extract
dry
extract
rapid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201510030471.1A
Other languages
Chinese (zh)
Other versions
CN104524000B (en
Inventor
卫强
李启照
杨春燕
华芳
李胜男
刘娟娟
吴甜甜
刘志
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Anhui Xinhua University
Original Assignee
Anhui Xinhua University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Anhui Xinhua University filed Critical Anhui Xinhua University
Priority to CN201510030471.1A priority Critical patent/CN104524000B/en
Publication of CN104524000A publication Critical patent/CN104524000A/en
Application granted granted Critical
Publication of CN104524000B publication Critical patent/CN104524000B/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • AHUMAN NECESSITIES
    • 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
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/81Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
    • A61K36/815Lycium (desert-thorn)
    • AHUMAN NECESSITIES
    • 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
    • A61K36/06Fungi, e.g. yeasts
    • A61K36/07Basidiomycota, e.g. Cryptococcus
    • A61K36/076Poria
    • AHUMAN NECESSITIES
    • 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
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/25Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258Panax (ginseng)
    • AHUMAN NECESSITIES
    • 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
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/28Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • AHUMAN NECESSITIES
    • 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
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/28Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/284Atractylodes
    • AHUMAN NECESSITIES
    • 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
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/28Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/287Chrysanthemum, e.g. daisy
    • AHUMAN NECESSITIES
    • 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
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/45Ericaceae or Vacciniaceae (Heath or Blueberry family), e.g. blueberry, cranberry or bilberry
    • AHUMAN NECESSITIES
    • 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
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/53Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/537Salvia (sage)
    • AHUMAN NECESSITIES
    • 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
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/73Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0002Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/2031Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/35Extraction with lipophilic solvents, e.g. Hexane or petrol ether
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/39Complex extraction schemes, e.g. fractionation or repeated extraction steps
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50Methods involving additional extraction steps
    • A61K2236/53Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50Methods involving additional extraction steps
    • A61K2236/55Liquid-liquid separation; Phase separation

Landscapes

  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Mycology (AREA)
  • Medical Informatics (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Microbiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

The invention discloses eyesight-improving fast release drop pills capable of rapidly improving visual fatigue and a preparation method thereof. The preparation method is characterized by being processed of lycium barbarum, salvia miltiorrhiza, panax pseudoginseng, huckleberry, chrysanthemum, chrysanthemum leaves, bighead atractylodes rhizome and poria cocos. The eyesight-improving fast release drop pills disclosed by the invention are convenient to use and high in compliance and are suitable for different people with visual fatigue.

Description

One can improve rapidly asthenopic improving eyesight rapid-released droppills and preparation method thereof
One, technical field
The present invention relates to one and can improve rapidly asthenopic improving eyesight rapid-released droppills and preparation method thereof, specifically a kind of with modern technology high efficiency extraction, purification active component, cause with drop pill and improve asthenopic a kind of function medicament fast.
Two, background technology
Along with popularizing of computer, mobile phone and network technology, people constantly extend between using at the moment, intensity increases, and asthenopic incidence rate increases year by year.Asthenopia is also known as eyestrain, with the conscious discomfort of eye for performance, occur and spirit, the psychological relevant organic syndrome changing into feature with eye or whole body, main manifestations is: discomfort or pain around eyeball and eye socket, keep in dark place, shed tears, eyes are dry and astringent, headache, Nausea and vomiting, the General Symptoms such as dizzy is there is time serious, and the mental symptoms such as often dispirited, drowsiness, the hypomnesis of spiritedness, insomnia.
The traditional Chinese medical science thinks that asthenopia is based on the hepatic and renal YIN deficiency, weakness of the spleen and stomach, qi depression to blood stasis, mistake eyesight, works with one's mind and overtaxes one's nerves, and is its predisposing factors." order is liver key ", " normal vision relying on sufficiency of liver-blood ".Say in " Qianjin Yao Fang seven apertures door " that the Tang Dynasty Sun Simiao is write: " its reading, game etc. person that excessively uses order, name day hepatic asthenia." in addition, the traditional Chinese medical science is thought " the emotion of the spleen being anxiety ", " anxiety impairing the spleen." the spleen being located in middle-JIAO is the mechanism of qi of mechanism of qi hinge, main the whole body, because of sitting, that mechanism of qi is run is smooth, disorder of QI movement renvoi dysfunction of the spleen in transportation.Current multimedia technology is highly developed, and people are often staring sees computer, mobile phone, simultaneously with thinking, memory, reasoning, excitement, worry, unhappiness, the thinking activities such as disgruntled.Excessive thinking, god coagulates in thing, and mechanism of qi is detained not all right, then easily increase the weight of the burden of middle burnt taste mechanism of qi hinge, injure spleen." the large puzzled opinion of Ling Shu Miraculous Pivot or Divine Axis " is pointed out: " the essence of five ZANG-organs and six FU-organs gas, notes in order all." the essence of five ZANG-organs and six FU-organs gas all relies temper and be able to up, if QI-insufficiency, can not on hold replenishing vital QI with drugs of warm nature order key, then look thing dim.
Improving eyesight rapid-released droppills medicine consists of Fructus Lycii, Radix Notoginseng, Radix Salviae Miltiorrhizae, Flos Chrysanthemi, chrysanthemum leaf, Pericarpium Citri tangerinae, Poria, the Rhizoma Atractylodis Macrocephalae.Fructus Lycii has nourishing the liver and kidney, replenishing vital essence to improve eyesight effect.Modern study shows, wolfberry pigment and polysaccharide are its improving eyesight main components.Radix Notoginseng total arasaponins is Radix Notoginseng principle active component, has blood vessel dilating and coronary artery, reduction peripheral vascular resistance, increases the effect such as cerebral blood flow and coronary flow, antithrombotic and anticoagulation.Radix Salviae Miltiorrhizae is blood circulation promoting and blood stasis dispelling important drugs, so-called " Radix Salviae Miltiorrhizae falls apart simply, the same SIWU TANG of merit ".The Sino-Philippines quinones composition of Radix Salviae Miltiorrhizae has coronary artery dilator, increases coronary flow, improves microcirculation, improve hemorheology status, effect such as protection erythrocyte membrane and anti-hypoxia etc.Pericarpium Citri tangerinae is Ericaceae Vaccinium plant, namely Europe be about used as eye health articles for use from nineteen sixty-five, its fruit procyanidins composition have improve vision, alleviate dizzy, promote to look regeneration of erythrocytes, improve noctovision, alleviate visual fatigue effect, its function of relieving visual fatigue mechanism mainly procyanidin acts on retinal isomerase, adds the generating rate of the photoactive substance " rhodopsin " of retinal visual cell.When rhodopsin is subject to light to amphiblestroid stimulation, in decomposing instantaneously, and this chemical change can be sent to brain, produce " visible ".The Rhizoma Atractylodis Macrocephalae is feverfew, and Shennong's Herbal is classified as top grade, has invigorating the spleen and benefiting QI, dampness diuretic effect.Poria is the dry sclerotia of On Polyporaceae Poria.Compendium of Material Medica is said: " Poria abnormal smells from the patient is light and ooze, and its property is up, born fluid, loosing the interspaces of skin and muscles ".Poria joined by the Rhizoma Atractylodis Macrocephalae, Rhizoma Atractylodis Macrocephalae spleen invigorating, and in relatively keeping, Poria eliminating dampness by diuresis, relatively descending, mutual reinforcement between is use, makes temper transporting and improving eyesight effect.Modern study shows, atractylodes lactone and triterpenes components are the material bases of the Rhizoma Atractylodis Macrocephalae and Poria invigorating the spleen and benefiting QI.
Drop pill is a kind of form of solid dispersion.Because it has the advantages such as stripping is fast, bioavailability is high, good effect, medicine stability are good.Drop pill mostly is sublingual administration, and medicine is directly absorbed by sublingual mucosa and enters blood circulation, avoids the oral liver first-pass effect that causes and medicine to lose in the degraded of gastric, makes high drug concentration arrive target organ, 5-15 minute rapid-onset.Rapid-released droppills is the pole tiny crystal grains of the solid dispersion drug formed under quenching conditions, therefore disintegrate is fast, and dissolution rate is fast, has quick-acting, efficient feature.
Three, summary of the invention
The present invention aims to provide one can improve rapidly asthenopic medicine and preparation method thereof, technical problem to be solved selects suitable medical material to carry out compatibility, utilize modern extraction, purification technique acquisition active component, utilize this kind of release dosage forms fast of rapid-released droppills, medicine is discharged into eye fast, improves rapidly asthenopia symptom.
Technical solution problem of the present invention adopts following technical scheme:
The present invention can improve rapidly asthenopic improving eyesight rapid-released droppills and be processed by the extract of the crude drug of following mass parts and adjuvant and obtain:
Wherein, described improving eyesight rapid-released droppills adjuvant used comprises Macrogol 2000, Macrogol 4000 and poloxamer188, and each adjuvant by the proportioning of mass parts is:
Macrogol 2000 3 ~ 4 parts;
Macrogol 4000 4 ~ 5 parts;
Poloxamer188 0.4-0.6 part.
Preferred mass part proportioning of each crude drug of improving eyesight rapid-released droppills of the present invention is:
On the basis of preferred mass part of each crude drug, preferred mass part proportioning of each adjuvant is:
Macrogol 2000 3.5 parts;
Macrogol 4000 4.5 parts;
Poloxamer188 0.5 part.
Improving eyesight rapid-released droppills of the present invention prepares by the following method:
1) dried wolfberry is got, pulverized 24 mesh sieves, add 3-5 times of volume by chloroform and the ether mixed liquor that forms of 1:1 by volume, extract 2-3 time with flash extracter, each 1-2min, merge extractive liquid, sucking filtration, after reclaiming the solvent in gained filtrate, by remove the filtrate after solvent 60 DEG C dry must to constant weight, obtain dry extract a, gained filter cake adds 8-10 times of volume distilled water to be continued to extract 3-4 time (voltage 70-90V) with flash extracter, each 2-3min, merge extractive liquid, sucking filtration, gained filtrate is concentrated into 15-20g/L, then micro-filtration membrane and ultrafilter membrane (operating pressure 0.15-0.20MPa) obtain trapped fluid excessively successively, 1/3-1/5 trapped fluid being concentrated into cumulative volume obtains concentrated solution, with n-butyl alcohol, chloroform and concentrated solution by volume 1:5:25 hybrid extraction remove deproteinize 5-6 time, subnatant 60 DEG C is dried to constant weight, obtain dry extract b.
2) dry Radix Salviae Miltiorrhizae and dry Radix Notoginseng is got, co-grinding crosses 100 mesh sieves, put into apparatus,Soxhlet's, add successively the petroleum ether of 10-15 times of volume, 10-15 times volume aether backflow 4-6h to colourless, discard petroleum ether liquid and ether solution, take out Radix Salviae Miltiorrhizae and pseudo-ginseng, 60 DEG C of dryings, the 90%-95% ethanol adding 15-20 times of volume carries out homogenate extraction 2-3 time (voltage 100-120V), extracts 2-3min at every turn, merge extractive liquid, sucking filtration, obtain filtrate A and filter cake A; The 65%-70% ethanol that filter cake A adds 15-20 times of volume again carries out homogenate extraction 2-3 time (voltage 100-120V), extracts 2-3min at every turn, merge extractive liquid, sucking filtration, obtains liquor B; Merging filtrate A and liquor B, recycling design, is dried to constant weight by the mixing filtrate 60 DEG C after removing solvent, obtains dry extract c;
3) Pericarpium Citri tangerinae fresh fruit is got, add 10-15 times of volume by mass concentration be the HCl of 2%-3% and methanol by volume 10:90 mix the mixed liquor formed and carry out homogenate extraction, extract 3-4 time (voltage 80-90V), each extraction 1-2min, sucking filtration, merging filtrate also crosses AB-8 type macroporous resin, with water elution to colourless, again with methanol-eluted fractions, meoh eluate 60 DEG C is dried to constant weight, obtains dry extract d.
4) dry Flos Chrysanthemi and chrysanthemum leaf is got, pulverized 24 mesh sieves, mixing, adds 75%-80% ethanol homogenate extraction 3-4 time (voltage 90-100V) of 10-15 times of volume, each 2-3min, merge extractive liquid, sucking filtration, gained filtrate is concentrated into 10-15g/L, then crosses micro-filtration membrane and ultrafilter membrane (operating pressure 0.20-0.22MPa) successively, discards trapped fluid, permeate 60 DEG C of dryings are dried to constant weight, obtain dry extract e.
5) the dry Rhizoma Atractylodis Macrocephalae and Poria is got, pulverized 60 mesh sieves, mixing, add 30-40 doubly by chloroform and the ether mixed liquid dipping 24-36h that forms of 1:1 by volume, with homogenate extraction 2-3 time (voltage 110-120V), each 3-4min, merge extractive liquid, sucking filtration, filtrate 60 DEG C is dried to constant weight, obtains dry extract f.
6) taking polyethylene glycol 2000, Macrogol 4000, poloxamer188 melting in 70 DEG C of water-baths, add dry extract a, dry extract b, dry extract c, dry extract d, dry extract e and dry extract f, stir certain hour, make it dispersed, in 80-85 DEG C of insulation, be placed in instillation in dropping-pill machine liquid chamber to be condensed into ball (condensation column length is 60cm, the distance of water dropper and condensed fluid is 6-8cm, liquid paraffin is coolant, drip speed to drip for 15-20 per minute, condensed fluid tip temperature is 70-80 DEG C, bottom temperature is 0-3 DEG C), after drop pill cools completely, take out drop pill, remove the liquid paraffin of surface attachment, put into the dry 24h of vacuum drying oven and get final product.
Compared with the prior art, beneficial effect of the present invention is embodied in:
The present invention is prepared into improving eyesight rapid-released droppills with Fructus Lycii, Radix Notoginseng, Radix Salviae Miltiorrhizae, Flos Chrysanthemi, chrysanthemum leaf, Pericarpium Citri tangerinae, Poria, Rhizoma Atractylodis Macrocephalae prescription.Homogenate extraction associating microfiltration-ultrafiltration purification technology is adopted to obtain wolfberry pigment, polysaccharide component in Fructus Lycii, adopt homogenate extraction-macroporous resin multiple techniques to obtain Pericarpium Citri tangerinae procyanidins composition, obtain Radix Salviae Miltiorrhizae quinone, Radix Notoginseng total arasaponins, atractylodes lactone composition and fuling triterpene constituents with homogenate extraction.Above composition is added Macrogol 2000, Macrogol 4000, poloxamer188, under quenching conditions, makes rapid-released droppills.Rapid-released droppills is the pole tiny crystal grains of the solid dispersion drug formed under quenching conditions, therefore disintegrate is fast, dissolution rate fast, can reach the object playing rapidly drug effect, have efficient, quick-acting feature.Easy to use, retinue's property is good, is applicable to having asthenopic different crowd to use.In addition, owing to containing total flavones, lactone, phenanthrenequione constituents in prescription, be insoluble in water, oral administration biaavailability is low, add Macrogol 2000, Macrogol 4000, poloxamer188 and above active constituents of medicine and make solid dispersion, form drop pill, significantly can increase dissolution, improve bioavailability in human body.Effect experiment shows, high, medium and low three the dosage groups of improving eyesight rapid-released droppills all obviously can reduce cGMP concentration in the impaired corpus ciliare tissue of black eye rabbit, and raise its cAMP concentration, prompting obviously can improve eye strain.Human experimentation shows that said preparation can improve juvenile hyperopia power, duration of photopic vision, significantly improves the symptoms such as ophthalmic bloated that experimenter eyestrain causes, ophthalmalgia, photophobia, blurred vision, eye be dry and astringent, without overt toxicity.
Four, detailed description of the invention
Embodiment 1:
1) dried wolfberry of 20 mass parts is got, pulverized 24 mesh sieves, add the chloroform-ether (1:1 of 3 times of volumes, V/V), extract 2 times with flash extracter, each 2min, merge extractive liquid, sucking filtration, after reclaiming the solvent in gained filtrate, dryly to constant weight, dry extract a must be obtained at 60 DEG C.Gained filter cake adds 8 times of volume distilled water and extracts 3 times (voltage 90V) with flash extracter, each 2min, merge extractive liquid, sucking filtration, gained filtrate is concentrated into 15g/L, and then micro-filtration membrane and ultrafilter membrane (operating pressure 0.15MPa) obtain trapped fluid excessively successively, and trapped fluid is concentrated into cumulative volume 1/4 obtains concentrated solution, with n-butyl alcohol-chloroform-concentrated solution (1:5:25, V/V) extraction removes deproteinize 5 times, and subnatant 60 DEG C is dried to constant weight, obtains dry extract b.
2) the dry Radix Salviae Miltiorrhizae of 10 mass parts and the dry Radix Notoginseng of 10 mass parts is got respectively, co-grinding crosses 100 mesh sieves, put into apparatus,Soxhlet's, add successively the petroleum ether of 10 times of volumes, 10 times of volumes aether backflow 6h to colourless, discard petroleum ether liquid and ether solution, take out Radix Salviae Miltiorrhizae and pseudo-ginseng, 60 DEG C of dryings, 95% ethanol adding 15 times of volumes carries out homogenate extraction 2 times (voltage 120V), extracts 3min at every turn, merge extractive liquid, sucking filtration, obtain filtrate A and filter cake A; 70% ethanol that filter cake A adds 15 times of volumes again carries out homogenate extraction 3 times (voltage 100V), extracts 2min at every turn, merge extractive liquid, sucking filtration, obtains liquor B; Merging filtrate A and liquor B, recycling design, 60 DEG C are dried to constant weight, obtain dry extract c;
3) the Pericarpium Citri tangerinae fresh fruit of 15 mass parts is got, the 2%HCl-methanol (10:90) adding 10 times of volumes carries out homogenate extraction, extract 3 times (voltage 90V), each extraction 1min, sucking filtration, merging filtrate crosses AB-8 type macroporous resin, with water elution to colourless, again with methanol-eluted fractions, meoh eluate 60 DEG C is dried to constant weight, obtains dry extract d.
4) the dry Flos Chrysanthemi of 15 mass parts and the dry chrysanthemum leaf of 15 mass parts is got, pulverized 24 mesh sieves, mixing, adds the 75%% ethanol homogenate extraction 3 times (voltage 100V) of 10 times of volumes, each 3min, merge extractive liquid, sucking filtration, gained filtrate is concentrated into 10g/L, then crosses micro-filtration membrane and ultrafilter membrane (operating pressure 0.20MPa) successively, discards trapped fluid, permeate 60 DEG C is dried to constant weight, obtains dry extract e.
5) the dry Rhizoma Atractylodis Macrocephalae of 10 mass parts and the dry Poria of 10 mass parts is got, pulverized 60 mesh sieves, mixing, the chlorofonn-ethylacetate (1:1, V/V) adding 30 times of volumes soaks 24h, with homogenate extraction 2 times (voltage 110V), each 4min, merge extractive liquid, sucking filtration, filtrate 60 DEG C is dried to constant weight, obtains dry extract f.
6) Macrogol 2000 of 3.5 mass parts is got, the Macrogol 4000 of 4.5 mass parts, poloxamer188 melting in 70 DEG C of water-baths of 0.5 mass parts, add dry extract a, dry extract b, dry extract c, dry extract d, dry extract e, dry extract f, stir certain hour, make it dispersed, in 80 DEG C of insulations, be placed in instillation in dropping-pill machine liquid chamber to be condensed into ball (condensation column length is 60cm, the distance of water dropper and condensed fluid is 8cm, liquid paraffin is coolant, dripping speed is 15 per minute, condensed fluid tip temperature is 70 DEG C, bottom temperature is 0 DEG C), after drop pill cools completely, take out drop pill, remove the liquid paraffin of surface attachment, put into the dry 24h of vacuum drying oven and get final product.
[test of pesticide effectiveness]
Test the impact of an improving eyesight rapid-released droppills on cAMP, cGMP content in rabbit corpus ciliare tissue
Cyclic adenosine monophosphate (Cyclic Adenosine Monophosphate, cAMP), cyclic guanosine monophosphate (Cyclic GuanosineMonophosphate, cGMP) be a pair Antagonism material, acted on by " second message,second messenger ", regulate the information transmission of hormone, neurotransmitter, participate in cellular metabolism link.The former cAMP promotes that fat and sugar unit decomposes, and strengthens myocardial contraction, and promote smooth muscle relaxation and suppress the effects such as platelet aggregation, the latter is then contrary.The two is contrary to the regulating action of cellular metabolism reaction and physiological function, and concentration change is correlated with mutually on the contrary.CAMP is formed with important meaning to prevention eyestrain, and it is mainly through improving sarcoplasmic reticulum to Ca 2+picked-up, reduce Ca in sarcoplasm 2+concentration, causes cell relaxation.Also by stimulating the phosphorylation of Smooth Muscle Myosin Light Chain Kinase, preventing myofilament from activating thus suppressing contractile response.
1 materials and methods
1.1 laboratory animal
2-2.5kg black eye rabbit, cleaning grade, is provided by Anhui University of Chinese Medecine's Experimental Animal Center.
1.2 experimental drug
The made improving eyesight rapid-released droppills of embodiment 1 (being made up of Fructus Lycii, Flos Chrysanthemi, Pericarpium Citri tangerinae, chrysanthemum leaf, Radix Salviae Miltiorrhizae, Radix Notoginseng), the heavy 0.03g of every ball.Contrast medicine is mulberry hemp pill is the accurate font size medicines of traditional Chinese medicines, and Huangshan Tianmu Pharmaceutical Co., Ltd. produces, lot number 20130506.This medicine is made up of Folium Mori, Semen Sesami Nigrum (stir-fry), has nourishing the liver and kidney, dispelling pathogenic wind for improving eyesight effect.For deficiency of the liver and kindey, dizziness and blurred vision, blurring of vision, epiphora induced by wind.Use this medicine in contrast, meet one of principle of positive control medicine setting, i.e. the accurate font size Chinese patent medicine of official approval or Western medicine.
1.3 experiment reagent
Rabbit cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) ELISA detection kit, be purchased from the Shanghai peaceful biological scientific research company limited of discipline, lot number: 130916.
1.4 key instrument
FSH-2 type is adjustable high speed refiner (Jiangsu Wei Nataike Instrument Ltd.), HH-S2 digital display thermostat water bath (Jin Cheng Guo Sheng experimental apparatus factory of Jintan City), SK-1-eddy mixer (Cheng Hui instrument plant of Jintan City), LD24-1.2 centrifuge (system in Beijing Jing founds company limited), WD-9417B microplate reader (Hangzhou remittance that instrument and equipment company limited), FA2004 electronic balance (Minqiao Precision Scientific Instruments Co., Ltd., Shanghai).
1.5 grouping and model are set up
Get the healthy black eye rabbit 60 of 2-2.5kg, be divided into normal saline group (normal saline at random, 10mL/kg), model group (normal saline, 10mL/kg), improving eyesight rapid-released droppills high (6.30g/kg), in (3.15g/kg), low (1.05g/kg) dosage group, mulberry hemp pill (1.25g/kg) positive controls.Often organize each 10, male and female half and half.Except normal saline group, other are respectively organized all with 30lux in daytime (illuminance), and night, 0lux carried out illumination, continuous illumination 10d.Continue to distinguish gastric infusion 2 weeks to the experimental rabbit after illumination, every day 2 times, administration volume is 10mL/kg.
1.6 index determining
After last administration 24h, put to death experimental rabbit with head-breaking, take out bilateral eyeball, be separated corpus ciliare, after rinsing well, filter paper blots, and weighs to eyes corpus ciliare.Again with refiner continuous homogenate 3 ~ 5 times in frozen water, each 10s, centrifuge 10 ~ 15min (low temperature low speed centrifuge 2000r/min), gets supernatant and adopts detection method shown in enzyme-linked immunosorbent assay (ELISA) reagent box to detect cAMP and cGMP content in rabbit corpus ciliare.
1.7 data statistics
With SPSS17.0 software statistics, between group data carry out Cochran & Cox be similar to t inspection.
2 results
The change of cAMP and cGMP in rabbit corpus ciliare tissue, as table 1.
The comparison (n=10) of cAMP and cGMP in corpus ciliare tissue between each group of table 1
Group cAMP(nmol/L) cGMP(nmol/L)
Normal saline group 128.82±2.26 36.02±2.85
Model group 51.20±2.06 122.65±3.71
Improving eyesight rapid-released droppills high dose group 115.86±3.79** 39.22±1.90*
Dosage group in improving eyesight rapid-released droppills 90.97±2.92** 50.18±3.62**
Improving eyesight rapid-released droppills low dose group 73.95±3.61** 62.06±2.84**
Mulberry hemp pill 89.11±2.74** 66.19±3.79**
Note: * represents compared with normal saline group, has significance (P<0.05); * represents compared with normal saline group, has pole significance (P<0.01); represent there is pole significance (P<0.01) compared with model group
As shown in Table 1, due to the impact of long-time illumination, excessively use eye, make ciliary muscle generation spastic contractions, in model group corpus ciliare tissue cAMP comparatively normal saline group obviously decline, cGMP comparatively normal saline group obviously raises, prompting eyes seriously impaired.Compare with model group, high, medium and low three the dosage groups of improving eyesight rapid-released droppills all can to make in model group cAMP in impaired corpus ciliare tissue obviously raise (P<0.01).From the cAMP concentration be elevated to, high, the middle dosage group of improving eyesight rapid-released droppills is better than mulberry hemp pill positive controls (89.11nmol/L).Compare with model group, high, medium and low three the dosage groups of improving eyesight rapid-released droppills all can to make in model group cGMP in impaired corpus ciliare tissue obviously reduce (P<0.01), from the cGMP concentration be reduced to, high, medium and low three the dosage groups of improving eyesight rapid-released droppills are all better than mulberry hemp pill positive controls (66.19nmol/L).
Test two improving eyesight rapid-released droppills and improve teenagers eyes fatigue experiment
1.1 experimental drug
The made improving eyesight rapid-released droppills of embodiment 1 (being made up of Fructus Lycii, Flos Chrysanthemi, Pericarpium Citri tangerinae, chrysanthemum leaf, Radix Salviae Miltiorrhizae, Radix Notoginseng, the Rhizoma Atractylodis Macrocephalae, Poria), every ball 0.30g.
1.2 key instrument
Urinate ten analysers; MXFA6100 type blood counting instrument; For the three-dimensional block chart of triangle disposition that legibility measures; E word standard near vision chart; Ophthalmofundoscope; GB standard visual acuity chart; Slit lamp; Trial lens set.
1.3 method
1.3.1 study subject choice criteria
18 ~ 35 years old age Computer worker 40, gets rid of following study subject: have infectivity, traumatic eye part disease; Suffer from cornea, crystal, vitreous body, retinopathy person; There are the disease patients such as cardiovascular and cerebrovascular vessel, liver, kidney, hemopoietic system; Take the medicine relevant with tested function, affect result judgement person; The medicine of long-term taking associated therapy vision, health product or use other treatment method to fail terminator etc.
1.3.2 experiment is divided into groups and is contrasted
Test-meal group and placebo group are set up in this test, often organize each 20 people, and test adopts and contrasts between self cross-reference and group.1.3.3 experimental technique
Give amount according to recommended amounts, the oral improving eyesight rapid-released droppills of test-meal group, every day 3 times, each 1, the placebo that the oral color of matched group, character are identical with Pericarpium Citri tangerinae extract improving eyesight rapid-released droppills, amount is with test-meal group, and duration of trial is 7d.
1.3.4 Testing index and project
Before and after experiment, indices is respectively measured once.Testing index and project have: general inspection (comprising subjective sensation, sleep state, mental status), body constitution inspection (physique, blood, urine, feces are conventional, blood parameters, B ultrasonic, chest x-ray and electrocardiogram), examination of eyes (subjective symptoms; The dry and astringent situation of ophthalmic bloated, ophthalmalgia, photophobia, blurred vision, eye).
Visuognosis persistence test formula: photopic vision time/watch attentively total time × 100%, minute is 2min, measures and averages for 2 times.Examination of visual acuity uses the inspection of GB visual acuity chart.Examination of near vision uses international near vision test type inspection.
By mild symptoms, in, heavily mark, statistics integrated value before and after experiment, serious symptom meter 3 points, moderate meter 2 points, slight meter 1 point.Each symptom is improved 1 and is divided into effectively, improves 2 and is divided into obviously, calculate symptom improvement rate.
1.3.5 date processing and result judge
With SPSS17.0 software statistics, between group data carry out Cochran & Cox be similar to t inspection.
Result judges: the rear test-meal group of test-meal test self compares and test-meal group compares with between matched group, symptom total mark, duration of photopic vision and total effective rate obviously improve, difference has significance and average duration of photopic vision raising is more than or equal to 0.1, thinks effective: what do not reach effective standard is invalid.Vision: naked vision is significantly improved (naked vision raising 0.2 or visual acuity chart inspection improve more than two row and think effective, and vision improves thinks invalid less than two row), and this is index for reference only.Medicine group compares with matched group statistical significant difference, can think to have and improve asthenopic health-care effect.
2 results
Compare before 2.1 experiments
40 experimenters, measure height, body weight before experiment, are divided into each 20 of medicine group, matched group at random.Medicine group male 12 example, women 8 example, 21.2 ± 1.0 years old mean age, average height and body weight are respectively 169.0 ± 5.6cm and 62.4 ± 6.1kg; Matched group male 15 example, women 5 example, 20.8 ± 1.6 years old mean age, average height and body weight are respectively 169.1 ± 5.3cm and 62.8 ± 4.9kg, through statistical test no significant difference (P>0.05).As shown in table 2, the photopic vision time between two groups, far visual acuity and symptom integral do not have significant difference (P>0.05) yet.
Front ordinary circumstance of observing table 2 compares (n=20, )
2.2 distant vision improves situation
As shown in table 3, matched group is compared with before experiment, and distant vision improves does not have significance to improve (P>0.05).Medicine group is compared with before experiment, and left eye has significance to improve (P<0.05), and right eye pole significance improves (P<0.01); Medicine group, compared with matched group, also presents left eye significance and improves (P<0.05), and right eye pole significance improves (P<0.01).
A table 3 liang group experiment front and back distant vision situation compares (n=20, )
Note: * represents that same group has significance (P<0.05) compared with before experiment; * represent with same group with experiment before compared with have pole significance (P<0.01); represent there is significance (P<0.05) compared with matched group; △ △represent there is pole significance (P<0.01) compared with matched group
2.3 durations of photopic vision improve situation
Medicine group is compared with before experiment, and duration of photopic vision has pole significance to improve (P<0.01); Medicine group is compared with matched group, and also presenting duration of photopic vision has pole significance to improve (P<0.01).In table 4.
The table 4 liang comparison that group experiment front and back duration of photopic vision changes (n=20, )
Group Before experiment After experiment Improve percentage rate/%
Positive group 51.79±9.65 68.12±6.11 ** 31.53
Matched group 52.84±8.02 51.98±9.21 -1.63
Note: * * represents that same group has pole significance (P<0.01) compared with before experiment, △ △represent there is pole significance (P<0.01) compared with matched group
2.4 symptoms improve situation
Medicine group experimenter ophthalmic bloated, ophthalmalgia, photophobia, blurred vision, the dry and astringent improvement rate of eye are significantly higher than matched group.The results are shown in Table 5, table 6.
Table 5 medicine group cardinal symptom improves situation
Symptom Case load Effective Effectively Invalid Improvement rate/%
Ophthalmic bloated 19 6 10 3 84.21
Ophthalmalgia 17 4 8 5 70.59
Photophobia 14 3 7 4 71.43
Blurred vision 16 5 8 3 81.25
Dry and astringent 16 8 6 2 87.50
Table 6 matched group cardinal symptom improves situation
Symptom Case load Effective Effectively Invalid Improvement rate/%
Ophthalmic bloated 15 0 1 14 6.67
Ophthalmalgia 14 0 2 12 14.29
Photophobia 16 1 2 13 18.75
Blurred vision 17 1 1 15 11.76
Dry and astringent 14 1 2 11 21.43
2.5 symptom integral statistics
Before and after the experiment of medicine group, clinical symptoms integration has significant difference (P<0.05), and reduction rate is 81.21%; And clinical symptoms integration there was no significant difference (P>0.05) before and after matched group experiment, reduction rate is only 8.07%, medicine group is compared with matched group, and clinical symptoms integration has significant difference (P<0.001).In table 7.
Table 7 clinical symptoms integration statistics (n=20, )
Group Before experiment After experiment Reduction rate/%
Medicine group 2.82±2.80 0.56±1.25** △△ 81.21
Matched group 2.85±2.01 2.62±1.32 8.07
Note: * * represents that same group has pole significance (P<0.01) compared with before experiment, △ △represent there is pole significance (P<0.01) compared with matched group
2.6 safety indexes are observed
Security inspection results contrast before and after test-meal, in table 8.Experimenter's B ultrasonic, chest x-ray and Electrocardioscopy no abnormality seen before test-meal.Before and after test-meal, the general physical examination of two groups of crowds, blood parameters and blood, urine, feces routine examination result are substantially in normal range.
Table 8 security inspection results contrast (n=20, )
Embodiment 2:
1) dried wolfberry of 20 mass parts is got, pulverized 24 mesh sieves, add the chloroform-ether (1:1 of 4 times of volumes, V/V), extract 3 times with flash extracter, each 1min, merge extractive liquid, sucking filtration, after reclaiming the solvent in gained filtrate, dryly to constant weight, dry extract a must be obtained at 60 DEG C.Gained filter cake adds 9 times of volume distilled water and extracts 3 times (voltage 80V) with flash extracter, each 3min, merge extractive liquid, sucking filtration, gained filtrate is concentrated into 18g/L, and then micro-filtration membrane and ultrafilter membrane (operating pressure 0.17MPa) obtain trapped fluid excessively successively, and trapped fluid is concentrated into cumulative volume 1/3 obtains concentrated solution, with n-butyl alcohol-chloroform-concentrated solution (1:5:25, V/V) extraction removes deproteinize 5 times, and subnatant 60 DEG C is dried to constant weight, obtains dry extract b.
2) the dry Radix Salviae Miltiorrhizae of 10 mass parts and the dry Radix Notoginseng of 10 mass parts is got respectively, co-grinding crosses 100 mesh sieves, put into apparatus,Soxhlet's, add successively the petroleum ether of 12 times of volumes, 12 times of volumes aether backflow 5h to colourless, discard petroleum ether liquid and ether solution, take out Radix Salviae Miltiorrhizae and pseudo-ginseng, 60 DEG C of dryings, 95% ethanol adding 15 times of volumes successively carries out homogenate extraction 3 times (voltage 110V), extracts 3min at every turn, merge extractive liquid, sucking filtration, obtain filtrate A and filter cake A; 65% ethanol that filter cake A adds 15 times of volumes again carries out homogenate extraction 2 times (voltage 110V), extracts 3min at every turn, merge extractive liquid, sucking filtration, obtains liquor B; Merging filtrate A and liquor B, recycling design, 60 DEG C are dried to constant weight, obtain dry extract c;
3) the Pericarpium Citri tangerinae fresh fruit of 15 mass parts is got, the 3%HCl-methanol (10:90) adding 12 times of volumes carries out homogenate extraction, extract 4 times (voltage 80V), each extraction 1min, sucking filtration, merging filtrate crosses AB-8 type macroporous resin, with water elution to colourless, again with methanol-eluted fractions, meoh eluate 60 DEG C is dried to constant weight, obtains dry extract d.
4) the dry Flos Chrysanthemi of 15 mass parts and the dry chrysanthemum leaf of 15 mass parts is got, pulverized 24 mesh sieves, mixing, adds the 80% ethanol homogenate extraction 4 times (voltage 95V) of 15 times of volumes, each 2min, merge extractive liquid, sucking filtration, gained filtrate is concentrated into 12g/L, then crosses micro-filtration membrane and ultrafilter membrane (operating pressure 0.21MPa) successively, discards trapped fluid, permeate 60 DEG C of dryings are dried to constant weight, obtain dry extract e.
5) the dry Rhizoma Atractylodis Macrocephalae of 10 mass parts and the dry Poria of 10 mass parts is got, pulverized 60 mesh sieves, mixing, the chlorofonn-ethylacetate (1:1, V/V) adding 30-40 times of volume soaks 28h, with homogenate extraction 3 times (voltage 110V), each 3min, sucking filtration, filtrate 60 DEG C of dryings are dried to constant weight, obtain dry extract f.
6) Macrogol 2000 of 3.5 mass parts is got, the Macrogol 4000 of 4.5 mass parts, poloxamer188 melting in 70 DEG C of water-baths of 0.5 mass parts, add dry extract a, dry extract b, dry extract c, dry extract d, dry extract e, dry extract f, stir certain hour, make it dispersed, in 85 DEG C of insulations, be placed in instillation in dropping-pill machine liquid chamber to be condensed into ball (condensation column length is 60cm, the distance of water dropper and condensed fluid is 6cm, liquid paraffin is coolant, dripping speed is 16 per minute, condensed fluid tip temperature is 75 DEG C, bottom temperature is 2 DEG C), after drop pill cools completely, take out drop pill, remove the liquid paraffin of surface attachment, put into the dry 24h of vacuum drying oven and get final product.
The present embodiment gained improving eyesight rapid-released droppills is through efficacy testing, identical with embodiment 1.
Embodiment 3:
1) dried wolfberry of 20 mass parts is got, pulverized 24 mesh sieves, add the chloroform-ether (1:1 of 5 times of volumes, V/V), extract 3 times with flash extracter, each 1min, merge extractive liquid, sucking filtration, after reclaiming the solvent in gained filtrate, dryly to constant weight, dry extract a must be obtained at 60 DEG C.Gained filter cake adds 10 times of volume distilled water and extracts 4 times (voltage 70V) with flash extracter, each 3min, merge extractive liquid, sucking filtration, gained filtrate is concentrated into 20g/L, and then micro-filtration membrane and ultrafilter membrane (operating pressure 0.20MPa) obtain trapped fluid excessively successively, and trapped fluid is concentrated into cumulative volume 1/5 obtains concentrated solution, with n-butyl alcohol-chloroform-concentrated solution (1:5:25, V/V) extraction removes deproteinize 6 times, and subnatant 60 DEG C is dried to constant weight, obtains dry extract b.
2) the dry Radix Salviae Miltiorrhizae of 10 mass parts and the dry Radix Notoginseng of 10 mass parts is got respectively, co-grinding crosses 100 mesh sieves, put into apparatus,Soxhlet's, add successively the petroleum ether of 10 times of volumes, 10 times of volumes aether backflow 6h to colourless, discard petroleum ether liquid and ether solution, take out Radix Salviae Miltiorrhizae and pseudo-ginseng, 60 DEG C of dryings, 90% ethanol adding 20 times of volumes successively carries out homogenate extraction 3 times (voltage 100V), extracts 2min at every turn, merge extractive liquid, sucking filtration, obtain filtrate A and filter cake A; 70% ethanol that filter cake A adds 20 times of volumes again carries out homogenate extraction 2 times (voltage 120V), extracts 3min at every turn, merge extractive liquid, sucking filtration, obtains liquor B; Merging filtrate A and liquor B, recycling design, 60 DEG C are dried to constant weight, obtain dry extract c;
3) the Pericarpium Citri tangerinae fresh fruit of 15 mass parts is got, the 3%HCl-methanol (10:90) adding 15 times of volumes carries out homogenate extraction, extract 4 times (voltage 80V), each extraction 1min, sucking filtration, merging filtrate crosses AB-8 type macroporous resin, with water elution to colourless, with methanol-eluted fractions, meoh eluate 60 DEG C is dried to constant weight, obtains dry extract d.
4) the dry Flos Chrysanthemi of 15 mass parts and the dry chrysanthemum leaf of 15 mass parts is got, pulverized 24 mesh sieves, mixing, adds the 75% ethanol homogenate extraction 4 times (voltage 90V) of 15 times of volumes, each 3min, merge extractive liquid, sucking filtration, gained filtrate is concentrated into 15g/L, then crosses micro-filtration membrane and ultrafilter membrane (operating pressure 0.22MPa) successively, discards trapped fluid, permeate 60 DEG C of dryings are dried to constant weight, obtain dry extract e.
5) the dry Rhizoma Atractylodis Macrocephalae of 10 mass parts and the dry Poria of 10 mass parts is got, pulverized 60 mesh sieves, mixing, the chlorofonn-ethylacetate (1:1, V/V) adding 40 times of volumes soaks 36h, with homogenate extraction 2 times (voltage 120V), each 4min, sucking filtration, filtrate 60 DEG C of dryings are dried to constant weight, obtain dry extract f.
6) Macrogol 2000 of 3.5 mass parts is got, the Macrogol 4000 of 4.5 mass parts, poloxamer188 melting in 70 DEG C of water-baths of 0.5 mass parts, add dry extract a, dry extract b, dry extract c, dry extract d, dry extract e, dry extract f, stir certain hour, make it dispersed, in 82 DEG C of insulations, be placed in instillation in dropping-pill machine liquid chamber to be condensed into ball (condensation column length is 60cm, the distance of water dropper and condensed fluid is 7cm, liquid paraffin is coolant, dripping speed is 20 per minute, condensed fluid tip temperature is 80 DEG C, bottom temperature is 3 DEG C), after drop pill cools completely, take out drop pill, remove the liquid paraffin of surface attachment, put into the dry 24h of vacuum drying oven and get final product.
The present embodiment gained improving eyesight rapid-released droppills is through efficacy testing, identical with embodiment 1.
Embodiment 4
1) dried wolfberry of 18 mass parts is got, pulverized 24 mesh sieves, add the chloroform-ether (1:1 of 3 times of volumes, V/V), extract 2 times with flash extracter, each 3min, merge extractive liquid, sucking filtration, after reclaiming the solvent in gained filtrate, dryly to constant weight, dry extract a must be obtained at 60 DEG C.Gained filter cake adds 8 times of volume distilled water and extracts 3 times (voltage 90V) with flash extracter, each 2min, merge extractive liquid, sucking filtration, gained filtrate is concentrated into 16g/L, and micro-filtration membrane and ultrafilter membrane (operating pressure 0.15MPa) obtain trapped fluid excessively respectively, and trapped fluid is concentrated into cumulative volume 1/4 obtains concentrated solution, with n-butyl alcohol-chloroform-concentrated solution (1:5:25, V/V) extraction removes deproteinize 5 times, and subnatant 60 DEG C is dried to constant weight, obtains dry extract b.
2) the dry Radix Salviae Miltiorrhizae of 8 mass parts and the dry Radix Notoginseng of 8 mass parts is got respectively, co-grinding crosses 100 mesh sieves, put into apparatus,Soxhlet's, add successively the petroleum ether of 10 times of volumes, 10 times of volumes aether backflow 4h to colourless, discard petroleum ether liquid and ether solution, take out Radix Salviae Miltiorrhizae and pseudo-ginseng, 60 DEG C of dryings, add 95% ethanol capable homogenate extraction 2 times (voltage 100V) of 15 times of volumes successively, extract 2min at every turn, merge extractive liquid, sucking filtration, obtain filtrate A and filter cake A; 70% ethanol that filter cake A adds 15 times of volumes again carries out homogenate extraction 3 times (voltage 110V), extracts 2min at every turn, merge extractive liquid, sucking filtration, obtains liquor B; Merging filtrate A and liquor B, recycling design, 60 DEG C are dried to constant weight, obtain dry extract c;
3) the Pericarpium Citri tangerinae fresh fruit of 13 mass parts is got, the 2%HCl-methanol (10:90) adding 10 times of volumes carries out homogenate extraction, extract 3 times (voltage 80V), each extraction 2min, sucking filtration, merging filtrate crosses AB-8 type macroporous resin, with water elution to colourless, with methanol-eluted fractions, meoh eluate 60 DEG C is dried to constant weight, obtains dry extract d.
4) the dry Flos Chrysanthemi of 13 mass parts and the dry chrysanthemum leaf of 13 mass parts is got, pulverized 24 mesh sieves, mixing, adds the 80% ethanol homogenate extraction 4 times (voltage 90V) of 10 times of volumes, each 2min, merge extractive liquid, sucking filtration, gained filtrate is concentrated into 10g/L, then crosses micro-filtration membrane and ultrafilter membrane (operating pressure 0.22MPa) successively, discards trapped fluid, permeate 60 DEG C of dryings are dried to constant weight, obtain dry extract e.
5) the dry Rhizoma Atractylodis Macrocephalae of 8 mass parts and the dry Poria of 8 mass parts is got, pulverized 60 mesh sieves, mixing, the chlorofonn-ethylacetate (1:1, V/V) adding 30 times of volumes soaks 24h, with homogenate extraction 3 times (voltage 110V), each 3min, sucking filtration, filtrate 60 DEG C of dryings are dried to constant weight, obtain dry extract f.
6) Macrogol 2000 of 3 mass parts is got, the Macrogol 4000 of 4 mass parts, poloxamer188 melting in 70 DEG C of water-baths of 0.4 mass parts, add dry extract a, dry extract b, dry extract c, dry extract d, dry extract e, dry extract f, stir certain hour, make it dispersed, in 84 DEG C of insulations, be placed in instillation in dropping-pill machine liquid chamber to be condensed into ball (condensation column length is 60cm, the distance of water dropper and condensed fluid is 7cm, liquid paraffin is coolant, dripping speed is 15 per minute, condensed fluid tip temperature is 70-80 DEG C, bottom temperature is 1 DEG C), after drop pill cools completely, take out drop pill, remove the liquid paraffin of surface attachment, put into the dry 24h of vacuum drying oven and get final product.
The present embodiment gained improving eyesight rapid-released droppills is through efficacy testing, identical with embodiment 1.
Embodiment 5
1) dried wolfberry of 22 mass parts is got, pulverized 24 mesh sieves, add the chloroform-ether (1:1 of 3 times of volumes, V/V), extract 3 times with flash extracter, each 2min, merge extractive liquid, sucking filtration, after reclaiming the solvent in gained filtrate, dryly to constant weight, dry extract a must be obtained at 60 DEG C.Gained filter cake adds 8 times of volume distilled water and extracts 3 times (voltage 90V) with flash extracter, each 2min, merge extractive liquid, sucking filtration, gained filtrate is concentrated into 15g/L, and then micro-filtration membrane and ultrafilter membrane (operating pressure 0.20MPa) obtain trapped fluid excessively successively, and trapped fluid is concentrated into cumulative volume 1/5 obtains concentrated solution, with n-butyl alcohol-chloroform-concentrated solution (1:5:25, V/V) extraction removes deproteinize 6 times, and subnatant 60 DEG C is dried to constant weight, obtains dry extract b.
2) the dry Radix Salviae Miltiorrhizae of 12 mass parts and the dry Radix Notoginseng of 12 mass parts is got respectively, co-grinding crosses 100 mesh sieves, put into apparatus,Soxhlet's, add successively the petroleum ether of 15 times of volumes, 15 times of volumes aether backflow 6h to colourless, discard petroleum ether liquid and ether solution, take out Radix Salviae Miltiorrhizae and pseudo-ginseng, 60 DEG C of dryings, 95% ethanol adding 20 times of volumes successively carries out homogenate extraction 3 times (voltage 120V), extracts 3min at every turn, merge extractive liquid, sucking filtration, obtain filtrate A and filter cake A; 65% ethanol that filter cake A adds 20 times of volumes again carries out homogenate extraction 2 times (voltage 120V), extracts 2min at every turn, merge extractive liquid, sucking filtration, obtains liquor B; Merging filtrate A and liquor B, recycling design, 60 DEG C are dried to constant weight, obtain dry extract c;
3) the Pericarpium Citri tangerinae fresh fruit of 17 mass parts is got, the 3%HCl-methanol (10:90) adding 15 times of volumes carries out homogenate extraction, extract 4 times (voltage 90V), each extraction 2min, sucking filtration, merging filtrate crosses AB-8 type macroporous resin, with water elution to colourless, with methanol-eluted fractions, meoh eluate 60 DEG C is dried to constant weight, obtains dry extract d.
4) the dry Flos Chrysanthemi of 17 mass parts and the dry chrysanthemum leaf of 17 mass parts is got, pulverized 24 mesh sieves, mixing, adds the 80% ethanol homogenate extraction 4 times (voltage 100V) of 15 times of volumes, each 3min, merge extractive liquid, sucking filtration, gained filtrate is concentrated into 15g/L, then crosses micro-filtration membrane and ultrafilter membrane (operating pressure 0.22MPa) successively, discards trapped fluid, permeate 60 DEG C of dryings are dried to constant weight, obtain dry extract e.
5) the dry Rhizoma Atractylodis Macrocephalae of 12 mass parts and the dry Poria of 12 mass parts is got, pulverized 60 mesh sieves, mixing, the chlorofonn-ethylacetate (1:1, V/V) adding 40 times of volumes soaks 36h, with homogenate extraction 3 times (voltage 120V), each 4min, sucking filtration, filtrate 60 DEG C of dryings are dried to constant weight, obtain dry extract f.
6) Macrogol 2000 of 4 mass parts is got, the Macrogol 4000 of 5 mass parts, poloxamer188 melting in 70 DEG C of water-baths of 0.6 mass parts, add dry extract a, dry extract b, dry extract c, dry extract d, dry extract e, dry extract f, stir certain hour, make it dispersed, in 82 DEG C of insulations, be placed in instillation in dropping-pill machine liquid chamber to be condensed into ball (condensation column length is 60cm, the distance of water dropper and condensed fluid is 6cm, liquid paraffin is coolant, dripping speed is 16 per minute, condensed fluid tip temperature is 80 DEG C, bottom temperature is 0 DEG C), after drop pill cools completely, take out drop pill, remove the liquid paraffin of surface attachment, put into the dry 24h of vacuum drying oven and get final product.
The present embodiment gained improving eyesight rapid-released droppills is through efficacy testing, identical with embodiment 1.

Claims (5)

1. can improve rapidly an asthenopic improving eyesight rapid-released droppills, it is characterized in that: described improving eyesight rapid-released droppills is processed by the extract of the crude drug of following mass parts and adjuvant and obtained:
2. according to claim 1ly can improve rapidly asthenopic improving eyesight rapid-released droppills, it is characterized in that:
Described improving eyesight rapid-released droppills adjuvant used comprises Macrogol 2000, Macrogol 4000 and poloxamer188, and each adjuvant by the proportioning of mass parts is:
Macrogol 2000 3 ~ 4 parts;
Macrogol 4000 4 ~ 5 parts;
Poloxamer188 0.4-0.6 part.
3. improving eyesight rapid-released droppills according to claim 1, is characterized in that: described improving eyesight rapid-released droppills is processed by the extract of the crude drug of following mass parts and adjuvant and obtained:
4. improving eyesight rapid-released droppills according to claim 3, is characterized in that:
Described improving eyesight rapid-released droppills adjuvant used comprises Macrogol 2000, Macrogol 4000 and poloxamer188, and each adjuvant by the proportioning of mass parts is:
Macrogol 2000 3.5 parts;
Macrogol 4000 4.5 parts;
Poloxamer188 0.5 part.
5. a preparation method for improving eyesight rapid-released droppills described in claim 1,2,3 or 4, is characterized in that operating according to the following steps:
1) dried wolfberry, pulverized 24 mesh sieves, add 3-5 times of volume by chloroform and the ether mixed liquor that forms of 1:1 by volume, extract 2-3 time with flash extracter, each 1-2min, merge extractive liquid, sucking filtration, reclaim the solvent in gained filtrate, constant weight is dried at 60 DEG C, obtain dry extract a, gained filter cake adds 8-10 times of volume distilled water to be continued to extract 3-4 time with flash extracter, each 2-3min, merge extractive liquid, sucking filtration, gained filtrate is concentrated into 15-20g/L, then micro-filtration membrane and ultrafilter membrane obtain trapped fluid excessively successively, 1/3-1/5 trapped fluid being concentrated into cumulative volume obtains concentrated solution, with n-butyl alcohol, chloroform and concentrated solution by volume 1:5:25 hybrid extraction remove deproteinize 5-6 time, subnatant 60 DEG C is dried to constant weight, obtain dry extract b,
2) dry Radix Salviae Miltiorrhizae and dry Radix Notoginseng is got, co-grinding crosses 100 mesh sieves, put into apparatus,Soxhlet's, add successively the petroleum ether of 10-15 times of volume, 10-15 times volume aether backflow 4-6h to colourless, discard petroleum ether liquid and ether solution, take out Radix Salviae Miltiorrhizae and pseudo-ginseng, 60 DEG C of dryings, the 90%-95% ethanol adding 15-20 times of volume carries out homogenate extraction 2-3 time, extracts 2-3min at every turn, merge extractive liquid, sucking filtration, obtain filtrate A and filter cake A; The 65%-70% ethanol that filter cake A adds 15-20 times of volume again carries out homogenate extraction 2-3 time, extracts 2-3min at every turn, merge extractive liquid, sucking filtration, obtains liquor B; Merging filtrate A and liquor B, recycling design, 60 DEG C are dried to constant weight, obtain dry extract c;
3) Pericarpium Citri tangerinae fresh fruit is got, add 10-15 times of volume by mass concentration be the HCl of 2%-3% and methanol by volume 10:90 mix the mixed liquor formed and carry out homogenate extraction, extract 3-4 time, each extraction 1-2min, sucking filtration, merging filtrate also crosses AB-8 type macroporous resin, with water elution to colourless, obtain meoh eluate with methanol-eluted fractions again, meoh eluate 60 DEG C is dried to constant weight, obtains dry extract d;
4) dry Flos Chrysanthemi and chrysanthemum leaf is got, pulverized 24 mesh sieves, mixing, adds 75%-80% ethanol homogenate extraction 3-4 time of 10-15 times of volume, each 2-3min, merge extractive liquid, sucking filtration, gained filtrate is concentrated into 10-15g/L, then crosses micro-filtration membrane and ultrafilter membrane successively, discards trapped fluid, permeate 60 DEG C is dried to constant weight, obtains dry extract e;
5) the dry Rhizoma Atractylodis Macrocephalae and Poria is got, pulverized 60 mesh sieves, mixing, add 30-40 times of volume by chloroform and the ether mixed liquid dipping 24-36h that forms of 1:1 by volume, with homogenate extraction 2-3 time, each 3-4min, merge extractive liquid, sucking filtration, filtrate 60 DEG C is dried to constant weight, obtains dry extract f;
6) taking polyethylene glycol 2000, Macrogol 4000, poloxamer188 melting in 70 DEG C of water-baths, add dry extract a, dry extract b, dry extract c, dry extract d, dry extract e and dry extract f, stir, in 80-85 DEG C of insulation, be placed in instillation in dropping-pill machine liquid chamber and be condensed into ball, after drop pill cools completely, take out drop pill, remove the liquid paraffin of surface attachment, put into the dry 24h of vacuum drying oven and get final product.
CN201510030471.1A 2015-01-21 2015-01-21 It is a kind of to improve improving eyesight rapid-released droppills of visual fatigue and preparation method thereof rapidly Expired - Fee Related CN104524000B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201510030471.1A CN104524000B (en) 2015-01-21 2015-01-21 It is a kind of to improve improving eyesight rapid-released droppills of visual fatigue and preparation method thereof rapidly

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201510030471.1A CN104524000B (en) 2015-01-21 2015-01-21 It is a kind of to improve improving eyesight rapid-released droppills of visual fatigue and preparation method thereof rapidly

Publications (2)

Publication Number Publication Date
CN104524000A true CN104524000A (en) 2015-04-22
CN104524000B CN104524000B (en) 2018-04-20

Family

ID=52839756

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201510030471.1A Expired - Fee Related CN104524000B (en) 2015-01-21 2015-01-21 It is a kind of to improve improving eyesight rapid-released droppills of visual fatigue and preparation method thereof rapidly

Country Status (1)

Country Link
CN (1) CN104524000B (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108853307A (en) * 2018-10-10 2018-11-23 赵翔 A kind of Chinese materia medica preparation for treating insufficiency of natural endowment type long sight
CN111700952A (en) * 2020-07-06 2020-09-25 右江民族医学院 A Chinese medicinal quick-release dripping pill for treating venomous snake bite, and its preparation method

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1178682A (en) * 1996-10-07 1998-04-15 郭书文 Chinese drug Mingmudan pill for improving eyesight and its producing method
CN1660226A (en) * 2004-12-29 2005-08-31 王四旺 'Wuzi Mingmu' pill and preparing technique
CN101347244A (en) * 2008-09-22 2009-01-21 曲建波 Health beverage
CN101406596A (en) * 2008-11-18 2009-04-15 李金伟 Medicament for treating dry eye
CN102091214A (en) * 2011-03-02 2011-06-15 朱宝民 Medicament for improving eyesight

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1178682A (en) * 1996-10-07 1998-04-15 郭书文 Chinese drug Mingmudan pill for improving eyesight and its producing method
CN1660226A (en) * 2004-12-29 2005-08-31 王四旺 'Wuzi Mingmu' pill and preparing technique
CN101347244A (en) * 2008-09-22 2009-01-21 曲建波 Health beverage
CN101406596A (en) * 2008-11-18 2009-04-15 李金伟 Medicament for treating dry eye
CN102091214A (en) * 2011-03-02 2011-06-15 朱宝民 Medicament for improving eyesight

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108853307A (en) * 2018-10-10 2018-11-23 赵翔 A kind of Chinese materia medica preparation for treating insufficiency of natural endowment type long sight
CN111700952A (en) * 2020-07-06 2020-09-25 右江民族医学院 A Chinese medicinal quick-release dripping pill for treating venomous snake bite, and its preparation method

Also Published As

Publication number Publication date
CN104524000B (en) 2018-04-20

Similar Documents

Publication Publication Date Title
CN101496865B (en) Chinese medicament preparation for treating depression and anxiety as well as preparation method thereof
CN103800670A (en) Traditional Chinese medicinal preparation for treating kidney-yang deficiency and preparation method thereof
CN103719493A (en) Brain-boosting and intelligence-enhancing sealwort health-care tea and preparation method thereof
CN104524000A (en) Eyesight-improving fast release drop pills capable of rapidly improving visual fatigue and preparation method thereof
CN102940785A (en) Traditional Chinese medicine composition for treating vertigo
CN101549085A (en) Traditional Chinese medicine for treating neurasthenia and preparation method thereof
CN102846871B (en) Chinese herbal preparation for treating liver-fire ascending type supraorbital neuralgia and preparation method thereof
CN103127466B (en) Chinese medicine decoction for treating cognitive disorder of Parkinson disease
CN112741890B (en) Traditional Chinese medicine composition for treating vertigo and preparation method thereof
CN104888158A (en) Folium apocyni veneti oral liquid for enhancing immunity and preparation method thereof
CN106237268B (en) It is a kind of to treat schizoid pharmaceutical composition and its application
CN102266428B (en) Anti-ageing Chinese medicinal composition and preparation method and application thereof
CN101530489A (en) Chinese medicine composition used for treating non-active stage infiltrative exophthalmos of thyroid-associated ophthalmopathy and preparation method thereof
CN107837384A (en) A kind of Chinese medicine composition for treating hand-foot-and-mouth disease
CN102727668B (en) Chinese medicine composition with effect of alleviating asthenopia and preparation method thereof
CN107648397B (en) Traditional Chinese medicine composition for treating liver-kidney yin deficiency and preparation method and application thereof
CN107029037A (en) It is a kind of to improve the eyesight-improving health care function patch of eyes based on nitric oxide principle
CN114010591A (en) Externally-applied traditional Chinese medicine gel paste for treating asthenopia and preparation method thereof
CN105311424B (en) A kind of Chinese medicine composition and preparation method thereof for treating visual fatigue
CN103990023A (en) Semen citri reticulatae sperm activating medicament and preparation method thereof
CN103495108A (en) Medicine for treating chronic hypotension and preparation method for medicine
CN103520610B (en) Traditional Chinese medicine composition for relieving asthenopia and preparation method thereof
CN102018789B (en) Traditional Chinese medicine composition for alleviating asthenopia and preparation method thereof
CN108079184A (en) Chinese medicine composition is preparing the application in preventing diabetic retinopathy drug
CN105920409A (en) Medicinal preparation for treating Alzheimer disease and application of medicinal preparation

Legal Events

Date Code Title Description
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20180420

Termination date: 20200121