CN107898827A - A kind of preparation method of hypoglycemic microballoon - Google Patents

A kind of preparation method of hypoglycemic microballoon Download PDF

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Publication number
CN107898827A
CN107898827A CN201711318483.XA CN201711318483A CN107898827A CN 107898827 A CN107898827 A CN 107898827A CN 201711318483 A CN201711318483 A CN 201711318483A CN 107898827 A CN107898827 A CN 107898827A
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hypoglycemic
preparation
small
microballoon
extract
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赵兴娟
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Suzhou Vocational Health College
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Suzhou Vocational Health College
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/63—Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Veterinary Medicine (AREA)
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  • Pharmacology & Pharmacy (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Cosmetics (AREA)

Abstract

The present invention provides a kind of preparation method of hypoglycemic microballoon, comprise the following steps：（1）By Chinese elm leaf crushed after being dried, sieving, refluxing extraction, takes filtrate, by filter residue refluxing extraction, takes filtrate, filtrate will merge to obtain extracting solution A twice；（2）Sweet osmanthus crushed after being dried is sieved, supercritical extract obtains extract B；（3）Squash polyoses, bitter melon polysaccharide, chitosan, calcium chloride, acetic acid and distilled water are mixed and dissolve to obtain solution C；（4）Extracting solution A, extract B and solution C are mixed, cross miillpore filter as spraying phase；（5）Using pectin, sodium tripolyphosphate, polysorbas20 and distilled water stirring and dissolving as condensed phase；（6）Spraying is mutually sprayed into condensed phase, tanshinone microsphere suspensions are obtained after curing, washing is drying to obtain.For the average grain diameter of microballoon prepared by the present invention at 30.42 μm 31.13 μm, containment is good, can discharge contained component for a long time, while have good blood sugar decreasing effect.

Description

A kind of preparation method of hypoglycemic microballoon
Technical field
The present invention relates to a kind of preparation method of hypoglycemic microballoon.
Background technology
As the improvement of people's living standards, the incidence of diabetes increases year by year, to people physiologically, mentally and Economically bring huge puzzlement.For example although insulin, sulfonylurea and biguanides can be in short-term for traditional hypoglycemic drug Blood glucose is reduced, but often produces some side effects, and it is possible to body is produced dependence.Therefore, researchers are more next It is directed to developing safer and economic hypoglycemic drug more.And the mechanism of drug therapy disease be by medicine with The interaction of internal lesions position, produces curative effect.Rational application method and dosage can improve the treatment effect of medicine Can, reduce toxic side effect.In order to avoid producing adverse reaction, traditional administering mode can only ensure that initial blood concentration can In the case of reaching therapeutic efficacy, dosage is reduced.But with the absorption of medicine, blood concentration reduces, and medicine just cannot continue Therapeutic effect is played, need to again be administered, great inconvenience is brought to patient, and when controlled drug delivery system can make blood concentration long Between control in optimal treatment scope, without frequent drug administration, in addition, drug sustained release system can maintain topically effective blood medicine dense for a long time Systemic administration is avoided while spending, reduces dosage and it also avoid injury to other normal structures of body.
The content of the invention
Technical problems to be solved：It is prepared the object of the present invention is to provide a kind of preparation method of hypoglycemic microballoon For the average grain diameter of microballoon at 30.42 μm -31.13 μm, containment is good, can discharge contained component for a long time, while has well Blood sugar decreasing effect.
Technical solution：A kind of preparation method of hypoglycemic microballoon, comprises the following steps：
（1）It will be crushed after 400g Chinese elm leaf clean dries, cross 60 mesh sieves, add 500-1000mL95% ethanol solutions at 85 DEG C When lower refluxing extraction 1-2 is small, take filtrate, by filter residue with 400-700mL95% ethanol solutions refluxing extraction 1-2 is small at 85 DEG C when, Filtrate is taken, filtrate will merge twice, and obtain extracting solution A；
（2）By 200g sweet osmanthus crushed after being dried, 60 mesh sieves, the supercritical extract at 35-40 DEG C of temperature, pressure 10-15MPa are crossed When 1-3 is small, extract B is obtained；
（3）By 30-60mg squash polyoses, 50-100mg bitter melon polysaccharides, 1-2g chitosans, 1-2g calcium chloride, 1-2ml acetic acid and 100-200ml distilled water, which is mixed, dissolves to obtain solution C；
（4）Extracting solution A, extract B and solution C are mixed, stirred 4-8 minutes under rotating speed 1500-2000r/min, crosses 0.22 μm miillpore filter is as spraying phase；
（5）1-3g pectin, 1-2g sodium tripolyphosphates, 0.5-1g polysorbas20s and 100-200ml distilled water are mixed, in rotating speed Stirring and dissolving is as condensed phase under 500-700r/min；
（6）Spraying is mutually sprayed into condensed phase, cure 5-6 it is small when after tanshinone microsphere suspensions, washing is drying to obtain.
Further, the deacetylation of the chitosan is 60%-70%.
Further, the preparation method of a kind of hypoglycemic microballoon, the step（1）Middle extraction time is 1.5 Hour.
Further, the preparation method of a kind of hypoglycemic microballoon, the step（2）Middle temperature is 37 DEG C, pressure Power is 13MPa, when extraction time is 2 small.
Further, the preparation method of a kind of hypoglycemic microballoon, the step（4）Middle rotating speed is 1600- 1900r/min, mixing time are 5-7 minutes.
Further, the preparation method of a kind of hypoglycemic microballoon, the step（5）Middle rotating speed is 600r/ min。
Further, the preparation method of a kind of hypoglycemic microballoon, the step（6）Middle hardening time is 5.5 Hour.
Beneficial effect：For its average grain diameter of hypoglycemic microballoon prepared by this method at 30.42 μm -31.13 μm, envelop rate is high Up to 46.5%, containment is good, in the release rate of the Chinese elm leaf extract of 24h, Flos Osmanthi Fragrantis extract, squash polyoses and bitter melon polysaccharide Difference minimum 50.7%, 53.2%, 41.4% and 44.2%, can discharge contained component for a long time, while diabetic mice is being taken Its blood glucose value significantly decreases after microballoon, has good blood sugar decreasing effect.
Embodiment
Embodiment 1
A kind of preparation method of hypoglycemic microballoon, comprises the following steps：
（1）To be crushed after 400g Chinese elm leaf clean dries, cross 60 mesh sieves, add 500mL95% ethanol solutions at 85 DEG C next time Stream extraction 1 it is small when, take filtrate, by filter residue with 400mL95% ethanol solutions refluxing extraction 1 is small at 85 DEG C when, filtrate is taken, by two Secondary filtrate merges, and obtains extracting solution A；
（2）By 200g sweet osmanthus crushed after being dried, 60 mesh sieves are crossed, when supercritical extract 1 is small at 35 DEG C of temperature, pressure 10MPa, Obtain extract B；
（3）30mg squash polyoses, 50mg bitter melon polysaccharides, 1g chitosans, 1g calcium chloride, 1ml acetic acid and 100ml distilled water are mixed Close stirring and dissolving and obtain solution C；
（4）Extracting solution A, extract B and solution C are mixed, stirred 4 minutes under rotating speed 1500r/min, crosses 0.22 μm of micropore Filter membrane is as spraying phase；
（5）1g pectin, 1g sodium tripolyphosphates, 0.5g polysorbas20s and 100ml distilled water are mixed, stirred under rotating speed 500r/min Mix dissolving and be used as condensed phase；
（6）Spraying is mutually sprayed into condensed phase, cure 5 it is small when after tanshinone microsphere suspensions, washing is drying to obtain.
Embodiment 2
A kind of preparation method of hypoglycemic microballoon, comprises the following steps：
（1）To be crushed after 400g Chinese elm leaf clean dries, cross 60 mesh sieves, add 600mL95% ethanol solutions at 85 DEG C next time Stream extraction 1.5 it is small when, take filtrate, by filter residue with 500mL95% ethanol solutions refluxing extraction 1.5 is small at 85 DEG C when, take filtrate, It filtrate will merge twice, and obtain extracting solution A；
（2）By 200g sweet osmanthus crushed after being dried, 60 mesh sieves are crossed, supercritical extract 1.5 is small at 36 DEG C of temperature, pressure 11MPa When, obtain extract B；
（3）40mg squash polyoses, 60mg bitter melon polysaccharides, 1.2g chitosans, 1.3g calcium chloride, 1.3ml acetic acid and 120ml are steamed Distilled water, which is mixed, dissolves to obtain solution C；
（4）Extracting solution A, extract B and solution C are mixed, stirred 5 minutes under rotating speed 1600r/min, crosses 0.22 μm of micropore Filter membrane is as spraying phase；
（5）1.5g pectin, 1.2g sodium tripolyphosphates, 0.6g polysorbas20s and 120ml distilled water are mixed, in rotating speed 550r/min Lower stirring and dissolving is as condensed phase；
（6）Spraying is mutually sprayed into condensed phase, cure 5.5 it is small when after tanshinone microsphere suspensions, washing is drying to obtain.
Embodiment 3
A kind of preparation method of hypoglycemic microballoon, comprises the following steps：
（1）To be crushed after 400g Chinese elm leaf clean dries, cross 60 mesh sieves, add 750mL95% ethanol solutions at 85 DEG C next time Stream extraction 1.5 it is small when, take filtrate, by filter residue with 550mL95% ethanol solutions refluxing extraction 1.5 is small at 85 DEG C when, take filtrate, It filtrate will merge twice, and obtain extracting solution A；
（2）By 200g sweet osmanthus crushed after being dried, 60 mesh sieves are crossed, when supercritical extract 2 is small at 37 DEG C of temperature, pressure 13MPa, Obtain extract B；
（3）45mg squash polyoses, 75mg bitter melon polysaccharides, 1.5g chitosans, 1.5g calcium chloride, 1.5ml acetic acid and 150ml are steamed Distilled water, which is mixed, dissolves to obtain solution C；
（4）Extracting solution A, extract B and solution C are mixed, stirred 6 minutes under rotating speed 1750r/min, crosses 0.22 μm of micropore Filter membrane is as spraying phase；
（5）2g pectin, 1.5g sodium tripolyphosphates, 0.75g polysorbas20s and 150ml distilled water are mixed, under rotating speed 600r/min Stirring and dissolving is as condensed phase；
（6）Spraying is mutually sprayed into condensed phase, cure 5.5 it is small when after tanshinone microsphere suspensions, washing is drying to obtain.
Embodiment 4
A kind of preparation method of hypoglycemic microballoon, comprises the following steps：
（1）It will be crushed after 400g Chinese elm leaf clean dries, cross 60 mesh sieves, added 90mL95% ethanol solutions and flow back at 85 DEG C Extract 1.5 it is small when, take filtrate, by filter residue with 600mL95% ethanol solutions refluxing extraction 1.5 is small at 85 DEG C when, take filtrate, will Filtrate merges twice, obtains extracting solution A；
（2）By 200g sweet osmanthus crushed after being dried, 60 mesh sieves are crossed, supercritical extract 2.5 is small at 39 DEG C of temperature, pressure 14MPa When, obtain extract B；
（3）50mg squash polyoses, 90mg bitter melon polysaccharides, 1.8g chitosans, 1.7g calcium chloride, 1.8ml acetic acid and 180ml are steamed Distilled water, which is mixed, dissolves to obtain solution C；
（4）Extracting solution A, extract B and solution C are mixed, stirred 7 minutes under rotating speed 1900r/min, crosses 0.22 μm of micropore Filter membrane is as spraying phase；
（5）2.5g pectin, 1.8g sodium tripolyphosphates, 0.9g polysorbas20s and 180ml distilled water are mixed, in rotating speed 650r/min Lower stirring and dissolving is as condensed phase；
（6）Spraying is mutually sprayed into condensed phase, cure 5.5 it is small when after tanshinone microsphere suspensions, washing is drying to obtain.
Embodiment 5
A kind of preparation method of hypoglycemic microballoon, comprises the following steps：
（1）To be crushed after 400g Chinese elm leaf clean dries, cross 60 mesh sieves, add 1000mL95% ethanol solutions at 85 DEG C next time Stream extraction 2 it is small when, take filtrate, by filter residue with 700mL95% ethanol solutions refluxing extraction 2 is small at 85 DEG C when, filtrate is taken, by two Secondary filtrate merges, and obtains extracting solution A；
（2）By 200g sweet osmanthus crushed after being dried, 60 mesh sieves are crossed, when supercritical extract 3 is small at 40 DEG C of temperature, pressure 15MPa, Obtain extract B；
（3）60mg squash polyoses, 100mg bitter melon polysaccharides, 2g chitosans, 2g calcium chloride, 2ml acetic acid and 200ml distilled water are mixed Close stirring and dissolving and obtain solution C；
（4）Extracting solution A, extract B and solution C are mixed, stirred 8 minutes under rotating speed 2000r/min, crosses 0.22 μm of micropore Filter membrane is as spraying phase；
（5）3g pectin, 2g sodium tripolyphosphates, 1g polysorbas20s and 200ml distilled water are mixed, stirred under rotating speed 700r/min Dissolving is used as condensed phase；
（6）Spraying is mutually sprayed into condensed phase, cure 6 it is small when after tanshinone microsphere suspensions, washing is drying to obtain.
The tablets in vitro experiment of drug bearing microsphere is what is carried out in the PBS buffer solutions of 0.01M.Specific experimentation It is：Above-mentioned drug bearing microsphere 80mg is accurately weighed, is respectively put into centrifuge tube, the PBS bufferings of 20 ml are then added into centrifuge tube Solution, will
4 × 3 centrifuge tubes are put into water-bath constant temperature oscillator（37 DEG C, 100 r/min）Middle vibration.Taken out after separated in time, Centrifugation, takes 3 ml of supernatant, and the PBS solution of same volume is added into centrifuge tube.Drug release to taking-up after the 24h that releases the drug is molten Liquid carries out ultraviolet test immediately, obtains the light absorption curve of medicine under the drug release time, and according to the extinction of maximum absorption wave strong point The math equation of degree and BSA standard curves, tries to achieve corresponding drug concentration.
The mouse for having determined as diabetes is divided into experimental group（Feeding embodiment 1-5, feeding dosage are 150mg/ KgBW, once a day）And blank control group, every group 10, mouse freely ingests, drinks water, and 12 h of animal indoor illumination is followed round the clock Ring, and maintain 22-25 DEG C of room temperature.Long run test 30 days, docking take blood, with the basal plasma glucose value of blood glucose meter measure mouse.
The partial properties index of hypoglycemic microballoon prepared by this method see the table below 1, it may be seen that its average grain diameter At 30.42 μm -31.13 μm, envelop rate is up to 46.5%, and containment is good, the Chinese elm leaf extract of 24h, Flos Osmanthi Fragrantis extract, The release rate of squash polyoses and bitter melon polysaccharide difference minimum 50.7%, 53.2%, 41.4% and 44.2%, can discharge contained for a long time Component, while diabetic mice its blood glucose value after microballoon is taken significantly decreases, and has good blood sugar decreasing effect.
The partial properties index of 1 hypoglycemic microballoon of table

Claims (7)

  1. A kind of 1. preparation method of hypoglycemic microballoon, it is characterised in that：Comprise the following steps：
    （1）It will be crushed after 400g Chinese elm leaf clean dries, cross 60 mesh sieves, add 500-1000mL95% ethanol solutions at 85 DEG C When lower refluxing extraction 1-2 is small, take filtrate, by filter residue with 400-700mL95% ethanol solutions refluxing extraction 1-2 is small at 85 DEG C when, Filtrate is taken, filtrate will merge twice, and obtain extracting solution A；
    （2）By 200g sweet osmanthus crushed after being dried, 60 mesh sieves, the supercritical extract at 35-40 DEG C of temperature, pressure 10-15MPa are crossed When 1-3 is small, extract B is obtained；
    （3）By 30-60mg squash polyoses, 50-100mg bitter melon polysaccharides, 1-2g chitosans, 1-2g calcium chloride, 1-2ml acetic acid and 100-200ml distilled water, which is mixed, dissolves to obtain solution C；
    （4）Extracting solution A, extract B and solution C are mixed, stirred 4-8 minutes under rotating speed 1500-2000r/min, crosses 0.22 μm miillpore filter is as spraying phase；
    （5）1-3g pectin, 1-2g sodium tripolyphosphates, 0.5-1g polysorbas20s and 100-200ml distilled water are mixed, in rotating speed Stirring and dissolving is as condensed phase under 500-700r/min；
    （6）Spraying is mutually sprayed into condensed phase, cure 5-6 it is small when after tanshinone microsphere suspensions, washing is drying to obtain.
  2. A kind of 2. preparation method of hypoglycemic microballoon according to claim 1, it is characterised in that：The de- second of the chitosan Acyl degree is 60%-70%.
  3. A kind of 3. preparation method of hypoglycemic microballoon according to claim 1, it is characterised in that：The step（1）In carry Take the time for 1.5 it is small when.
  4. A kind of 4. preparation method of hypoglycemic microballoon according to claim 1, it is characterised in that：The step（2）Medium temperature Spend for 37 DEG C, pressure 13MPa, when extraction time is 2 small.
  5. A kind of 5. preparation method of hypoglycemic microballoon according to claim 1, it is characterised in that：The step（4）Transfer Speed is 1600-1900r/min, and mixing time is 5-7 minutes.
  6. A kind of 6. preparation method of hypoglycemic microballoon according to claim 1, it is characterised in that：The step（5）Transfer Speed is 600r/min.
  7. A kind of 7. preparation method of hypoglycemic microballoon according to claim 1, it is characterised in that：The step（6）In it is solid When the change time is 5.5 small.
CN201711318483.XA 2017-12-12 2017-12-12 A kind of preparation method of hypoglycemic microballoon Pending CN107898827A (en)

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Application publication date: 20180413