CN106581692A - Ziyuglycoside I inclusion compound and preparation method thereof - Google Patents
Ziyuglycoside I inclusion compound and preparation method thereof Download PDFInfo
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- CN106581692A CN106581692A CN201610892641.1A CN201610892641A CN106581692A CN 106581692 A CN106581692 A CN 106581692A CN 201610892641 A CN201610892641 A CN 201610892641A CN 106581692 A CN106581692 A CN 106581692A
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- ziyuglycoside
- cyclodextrin
- hydroxypropylβ
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- clathrate
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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
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
- A61K36/739—Sanguisorba (burnet)
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- Animal Behavior & Ethology (AREA)
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- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
The invention provides a ziyuglycoside I inclusion compound, which is prepared from the raw and auxiliary materials including, by weight, 1 part of ziyuglycoside I, and 1-30 parts of hydroxypropyl beta-cyclodextrin. The hydroxypropyl beta-cyclodextrin is used as an inclusion material, so a high-quality ziyuglycoside I inclusion compound can be produced with inclusive rate reaching 91.5%. An efficacy test proves that the ziyuglycoside I inclusion compound, compared with a model group, can significantly increase the number of WBC, RBC, PLT, NEUT and HGB in peripheral blood, wherein the efficacy of the inclusion compound is better than ziyuglycoside I raw drug, so that when the ziyuglycoside I is processed into the inclusion compound, the bioavailability of the main drug is increased, thereby improving the effect thereof for increasing the number of hemocytes and preventing and treating myelosuppression.
Description
Technical field
The present invention relates to a kind of Ziyuglycoside I clathrate and preparation method thereof, belongs to drug world.
Background technology
Bone marrow depression is clinically common disease of hematopoietic system, and it can betide the radiation of each system tumor disease and control
Treat and (or) chemotherapy, ionizing radiation cause radiation injury, viral hepatitis, piconaviruses infection or medicine (chloromycetin,
Benzene, sulfanilamide, anti-insane carbuncle medicine, tranquilizer, antithyroid drug, antidiabetic drug, malaria, sleeping pill) etc. factor.Bone marrow depression can
Cause the damage of bone marrow microenvironment, hematopoietic stem cell, hematopoietic cell growth factor etc., grain, red, megakaryocytic series unification system, two
It is or three is that cell is suppressed.Agranulocytosises can cause severe infections；Erythrocyte is significantly reduced can cause severe anemia；Blood is little
Plate is decreased obviously and causes severe haemorrhage, even results in death.At present, clinically for bone marrow depression still lacks effectively treatment handss
Section, needs badly and develops the preferable medicine of drug effect.
Sanguisorbin I, English name ziyu-glycoside I, CAS 35286-58-9 are from Rosaceae Radix Sanguisorbae platymiscium
The compound with pharmacologically active for obtaining is extracted in the root of Radix Sanguisorbae or the Radix Sanguisorbae that comes into leaves.CN101119740A discloses sanguisorbin
I purposes in the medicine for raising erythrocyte and hemoglobin is prepared.However, actually used middle discovery, sanguisorbin I drug effect is owed
It is good, often it is difficult to obtain preferable hemocytes increasing level, the effect for the treatment of bone marrow depression during exclusive use.Therefore, need badly and carry
The drug effect of high sanguisorbin I, promotes medicine application clinically.
The content of the invention
It is an object of the invention to provide a kind of sanguisorbin I clathrate and preparation method thereof.
The invention provides a kind of Ziyuglycoside I clathrate, it is prepared from by the supplementary material of following weight proportioning：Ground
1 part of elm saponin I, 1～30 part of hydroxypropylβ-cyclodextrin.
Further, it is prepared from by the supplementary material of following weight proportioning：1 part of Ziyuglycoside I, hydroxypropyl beta-ring
1～20 part of dextrin.
Further, it is prepared from by the supplementary material of following weight proportioning：1 part of Ziyuglycoside I, hydroxypropyl beta-ring
20 parts of dextrin.
The invention provides a kind of preparation method of the clathrate, comprises the steps：
A, sanguisorbin I, hydroxypropylβ-cyclodextrin be dissolved in organic solvent respectively, obtain sanguisorbin I solution, hydroxyl
Propyl group beta-schardinger dextrin-solution, it is standby；
B, sanguisorbin I solution is added in hydroxypropylβ-cyclodextrin solution, mix homogeneously；
C, the organic solvent removed in b step gained mixture, crush, and obtain final product.
Further, the organic solvent described in a steps is dehydrated alcohol.
Further, sanguisorbin I and the mass volume ratio of solvent are 1 in the sanguisorbin I solution described in a steps：
100；Hydroxypropylβ-cyclodextrin and the mass volume ratio of solvent are 1 in described hydroxypropylβ-cyclodextrin solution：10.
Further, b step is by sanguisorbin I and hydroxypropylβ-cyclodextrin solution mixing 4h.
Further, mixture is placed in solvent evaporated on 60 DEG C of water-baths by step c.
The invention provides the Ziyuglycoside I clathrate is in hemocytes increasing, the medicine of amount of hemoglobin is prepared
Purposes.
The invention provides use of the Ziyuglycoside I clathrate in the medicine for preparing treatment and/or prevention bone marrow depression
On the way.
The invention provides a kind of sanguisorbin I clathrate.Inventor has found that sanguisorbin I is raised in research process
The reason for blood cell levels less effective is that its dissolubility is low, gastrointestinal absorption rate is little, cause the bioavailability of the medicine compared with
It is low, limit the performance of its drug effect.Sanguisorbin I can be prepared into quality by the present invention with hydroxypropylβ-cyclodextrin to include material
Preferable clathrate, inclusion rate is up to 91.5%.In effect experiment, compare with model group, sanguisorbin I clathrate energy of the present invention
Peripheral blood WBC, RBC, PLT, NEUT and HGB quantity is significantly raised, and drug effect is substantially better than sanguisorbin I active compound, shows this
It is bright that sanguisorbin I is prepared into after clathrate the bioavailability that can improve principal agent, strengthen its hemocytes increasing quantity, preventing and treating
The effect of bone marrow depression.
Obviously, the above of the invention, according to the ordinary technical knowledge and customary means of this area, without departing from
Under the premise of the above-mentioned basic fundamental thought of the present invention, the modification of other various ways can also be made, is replaced or is changed.
By the following examples the specific embodiment of form, remakes further specifically to the above of the present invention
It is bright.But this scope for being interpreted as above-mentioned theme of the invention should not be only limitted to Examples below.It is all based on the above of the present invention
The technology realized belongs to the scope of the present invention.
Specific embodiment
Raw material, equipment used in the specific embodiment of the invention is known product, is obtained by buying commercially available prod.
The preparation of the sanguisorbin I clathrate of the present invention of embodiment 1
Prescription：Ziyuglycoside I 5g, hydroxypropylβ-cyclodextrin 10g.
Preparation method：The Ziyuglycoside I of recipe quantity is taken, plus the dehydrated alcohol ultrasound of 100 times of volumes obtains solution to dissolving
1.Recipe quantity hydroxypropyl beta-CD is separately taken, adds the dehydrated alcohol ultrasound of 10 times of volumes to dissolving, obtain solution 2.Solution 2 is placed on
Stir in constant temperature blender with magnetic force, while solution 1 is slowly added in solution 2 with dropper, when solution 1 all add solution 2 it
Afterwards, its mixed liquor is allowed to stir in constant temperature blender with magnetic force four hours.Mixed liquor is poured in evaporating dish, 60 DEG C of water-baths are placed on
On, it is evaporated, take and be evaporated that thing is finely ground to obtain clathrate.
Beneficial effects of the present invention are proved below by way of experimental example.
Experimental example 1 prepares the quality evaluation of Ziyuglycoside I clathrate using different inclusion materials
This experiment prepares Radix Sanguisorbae soap with beta-schardinger dextrin-, methyl beta-cyclodextrin, hydroxypropylβ-cyclodextrin to include material respectively
Glycosides I clathrates.
Supplementary material proportioning：Ziyuglycoside I 5g, inclusion material 10g.
Preparation method：The Ziyuglycoside I of recipe quantity is taken, plus 100 times of volume dehydrated alcohol ultrasounds obtain solution 1 to dissolving.
Inclusion material is separately taken, adds 10 times of volume dehydrated alcohol ultrasounds to dissolving, obtain solution 2.Solution 2 is placed on into temperature constant magnetic stirring
Stir on device, while solution 1 is slowly added in solution 2 with dropper, after solution 1 all adds solution 2, allow its mixed liquor
Stir four hours in constant temperature blender with magnetic force.Mixed liquor is poured in evaporating dish, is placed on 60 DEG C of water-baths, be evaporated, take steaming
Dry is finely ground to obtain clathrate, surveys its inclusion rate (quality/Ziyuglycoside I of Ziyuglycoside I in inclusion rate (%)=clathrate
Dispensing quality × 100%).Ziyuglycoside I content is determined using HPLC methods, chromatographic condition：Agilent extend-C18 chromatographs
Post (250 × 4.6mm, 5 μm), flow velocity：1.0mL·min-1；Column temperature：30℃；Sample size：10μL；With acetonitrile-water (30:70) it is
Mobile phase；Detection wavelength is 208nm.The results are shown in Table 1.
The different inclusion materials of table 1 prepare the quality evaluation of Ziyuglycoside I clathrate
Experimental result：It is up to hydroxypropylβ-cyclodextrin to include Ziyuglycoside I clathrate prepared by material, inclusion rate
90.5%, include best results；Can cause inclusion rate if the inclusion material such as beta-schardinger dextrin-, methyl beta-cyclodextrin of other species
It is remarkably decreased.
Result above shows, only when using present invention inclusion material hydroxypropylβ-cyclodextrin, the Radix Sanguisorbae for preparing
Saponin I inclusion amount of substance is optimal.
Experimental example 2 includes the impact that material usage includes amount of substance to sanguisorbin I
Weight proportion according to table 2, weighs respectively Ziyuglycoside I, the hydroxypropylβ-cyclodextrin of different proportion, presses
State method test：Ziyuglycoside I is taken, plus the dehydrated alcohol ultrasound of 100 times of volumes obtains solution 1 to dissolving.Separately take hydroxypropyl beta-
Cyclodextrin, adds the dehydrated alcohol ultrasound of 10 times of volumes to dissolving, and obtains solution 2.Solution 2 is placed in constant temperature blender with magnetic force
Stirring, while solution 1 is slowly added in solution 2 with dropper, after solution 1 all adds solution 2, allows its mixed liquor in perseverance
Stir four hours on warm magnetic stirring apparatuss.Mixed liquor is poured in evaporating dish, is placed on 60 DEG C of water-baths, be evaporated, taken and be evaporated thing
It is finely ground to obtain clathrate, survey its inclusion rate.The results are shown in Table 2.
The Ziyuglycoside I clathrate inclusion rate measurement result of table 2
Experimental result：It is preferable that hydroxypropylβ-cyclodextrin consumption can prepare quality when being 1-30 times of sanguisorbin I
Clathrate, inclusion rate can reach more than 83%；Supplementary material consumption outside this range, such as experimental group 1, inclusion rate then significantly under
Drop, it is impossible to obtain up-to-standard product.When hydroxypropylβ-cyclodextrin consumption is 1-20 times of sanguisorbin I, the quality of the pharmaceutical preparations is obtained
Further optimization, inclusion rate is improved to more than 90%；Wherein, in sanguisorbin I：Hydroxypropylβ-cyclodextrin mass ratio is 1：20
Under conditions of, inclusion rate is up to 91.5%.
The pharmacodynamic study of the Ziyuglycoside I clathrate of the present invention of experimental example 3
1. experiment material
1.1 test medicine：Ziyuglycoside I-hydroxypropyl beta-CD inclusion (preparing according to embodiment 1), Ziyuglycoside I, ring
Phosphamide.
1.2 laboratory animal：KM- mices：18.5～22.5g.
1.3 experimental apparatus：Full-automatic blood cell analysis machine；BS-600L electronic balances：Specification：600g/0.1g, Shanghai friend's sound
Weighing apparatus company limited.
1.4 statistical method
Statistical analysiss are carried out with the softwares of SPSS 17.0.Data are with mean ± standard deviationRepresent, Dan Yin is adopted between group
Plain variance analyses, carry out LSD inspections between the neat person's group of variance, heterogeneity of variance person carries out Tamhane ' s T2 inspections.
2. experimental technique
2.1 laboratory animals are grouped and prepared by model
All Animal adaptabilities are randomly divided into after feeding 1 week by body weight：Blank group；Model group；Ziyuglycoside I-hydroxypropyl
Beta-CD inclusion group, is configured to 0.5mgkg-1,2.5mgkg-1,10mgkg-1 suspension, prepared before use；Radix Sanguisorbae soap
Glycosides I groups；10%DMSO- physiological saline solutions are used, 0.5mgkg-1,2.5mgkg-1,10mgkg-1 suspension is configured to,
Prepared before use.Test the 1st day, in addition to blank group, remaining each group mice presses 50mgkg-1 dosage intraperitoneal injection of cyclophosphamide
Normal saline solution, for three days on end, naive mice tail vein injection equal-volume normal saline.
2.2 administration
Each experimental group from test the 1st day start according to dosage, administering mode give relative medicine, blank group and model group mice
Gastric infusion equal-volume normal saline, continuous 7 days.
2.3 collection of specimens
Test the 8th day, each experimental mice eye socket takes blood, collect to be measured with the 0.5mlEP pipes equipped with EDTA anticoagulant.
2.4 Testing index and method
Peripheral hemogram is detected：Using full-automatic blood counting instrument to each experimental mice peripheral blood leucocyte (WBC), neutrality
Granulocyte (NEUT) erythrocyte (RBC), platelet (PLT), hemoglobin (HGB) are counted.
3. experimental result
The each experimental mice peripheral blood hemocyte quantity of table 3
Note：Compare with model group, * P<0.05, * * P<0.01；Compare with Ziyuglycoside I group, △ P<0.05, △ △ P<
0.01。
As a result show, compare with model group, Ziyuglycoside I of the present invention-hydroxypropyl beta-CD inclusion group mouse peripheral blood
WBC, RBC, PLT quantity has significantly raise (P<0.05), there was no significant difference for Ziyuglycoside I group；With Ziyuglycoside I group ratio
Compared with Ziyuglycoside I of the present invention-hydroxypropyl beta-CD inclusion group mouse peripheral blood WBC, RBC, PLT quantity has significantly raise (P<
0.05)。
The each experimental mice peripheral blood hemocyte quantity of table 4
Note：Compare with model group, * P<0.05, * * P<0.01；Compare with Ziyuglycoside I group, △ P<0.05, △ △ P<
0.01。
As a result show, compare with model group, Ziyuglycoside I of the present invention-hydroxypropyl beta-CD inclusion group mouse peripheral blood
NEUT and HGB quantity has significantly raise (P<0.05), there was no significant difference for Ziyuglycoside I group；Compare with Ziyuglycoside I group,
Ziyuglycoside I of the present invention-hydroxypropyl beta-CD inclusion group mouse peripheral blood NEUT and HGB quantity has significantly raise (P<
0.05)。
Claims (10)
1. a kind of Ziyuglycoside I clathrate, is characterized in that：It is prepared from by the supplementary material of following weight proportioning：Radix Sanguisorbae soap
1 part of glycosides I, 1～30 part of hydroxypropylβ-cyclodextrin.
2. clathrate as claimed in claim 1, is characterized in that：It is prepared from by the supplementary material of following weight proportioning：Ground
1 part of elm saponin I, 1～20 part of hydroxypropylβ-cyclodextrin.
3. clathrate as claimed in claim 2, is characterized in that：It is prepared from by the supplementary material of following weight proportioning：Ground
1 part of elm saponin I, 20 parts of hydroxypropylβ-cyclodextrin.
4. a kind of preparation method of clathrate described in claims 1 to 3 any one, is characterized in that：Comprise the steps：
A, sanguisorbin I, hydroxypropylβ-cyclodextrin be dissolved in organic solvent respectively, obtain sanguisorbin I solution, hydroxypropyl
Beta-schardinger dextrin-solution, it is standby；
B, sanguisorbin I solution is added in hydroxypropylβ-cyclodextrin solution, mix homogeneously；
C, the organic solvent removed in b step gained mixture, crush, and obtain final product.
5. preparation method as claimed in claim 4, is characterized in that：Organic solvent described in a steps is dehydrated alcohol.
6. the preparation method as described in claim 4 or 5, is characterized in that：Radix Sanguisorbae soap in sanguisorbin I solution described in a steps
Glycosides I is 1 with the mass volume ratio of solvent：100；Hydroxypropylβ-cyclodextrin and solvent in described hydroxypropylβ-cyclodextrin solution
Mass volume ratio is 1：10.
7. preparation method as claimed in claim 4, is characterized in that：B step is by sanguisorbin I and hydroxypropylβ-cyclodextrin solution
Mixing 4h.
8. preparation method as claimed in claim 4, is characterized in that：Step c mixture is placed on 60 DEG C of water-baths be evaporated it is molten
Agent.
9. Ziyuglycoside I clathrate described in claims 1 to 3 any one is preparing hemocytes increasing, amount of hemoglobin
Purposes in medicine.
10. Ziyuglycoside I clathrate described in claims 1 to 3 any one is preparing treatment and/or is preventing the medicine of bone marrow depression
The purposes of thing.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2015106707735 | 2015-10-16 | ||
| CN201510670773 | 2015-10-16 |
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| CN106581692A true CN106581692A (en) | 2017-04-26 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107261157A (en) * | 2017-06-14 | 2017-10-20 | 苏州大学 | Inclusion compound of blueberry leaf melanin and its preparation method and application |
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|---|---|---|---|---|
| CN101138545A (en) * | 2006-09-08 | 2008-03-12 | 广州天安医药科技有限公司 | Clathrate compound containing ginsenoside Rg2 and method of preparing the same |
| CN101119740B (en) * | 2004-12-14 | 2012-02-29 | 成都地奥制药集团有限公司 | Use of radix sanguisorbae and its extract for preparing medicament to increase RBC and hemoglobin |
-
2016
- 2016-10-13 CN CN201610892641.1A patent/CN106581692A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101119740B (en) * | 2004-12-14 | 2012-02-29 | 成都地奥制药集团有限公司 | Use of radix sanguisorbae and its extract for preparing medicament to increase RBC and hemoglobin |
| CN101138545A (en) * | 2006-09-08 | 2008-03-12 | 广州天安医药科技有限公司 | Clathrate compound containing ginsenoside Rg2 and method of preparing the same |
Non-Patent Citations (1)
| Title |
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| 高小平等: "地榆促造血作用的有效部位筛选", 《中国天然药物》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107261157A (en) * | 2017-06-14 | 2017-10-20 | 苏州大学 | Inclusion compound of blueberry leaf melanin and its preparation method and application |
| CN107261157B (en) * | 2017-06-14 | 2020-01-10 | 苏州大学 | Inclusion compound of vaccinium bracteatum leaf melanin and preparation method and application thereof |
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