CN1187092C - Slow-released carrier with nano structure for drug - Google Patents
Slow-released carrier with nano structure for drug Download PDFInfo
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- CN1187092C CN1187092C CNB011340827A CN01134082A CN1187092C CN 1187092 C CN1187092 C CN 1187092C CN B011340827 A CNB011340827 A CN B011340827A CN 01134082 A CN01134082 A CN 01134082A CN 1187092 C CN1187092 C CN 1187092C
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- slow
- carrier
- release
- hydroxyapatite
- calcium carbonate
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Abstract
本发明是一种用于药物的具有纳米结构的缓释载体，它涉及具有药物缓释作用的载体材料。该载体是由软体动物的具有碳酸钙成分和文石结构的硬组织改性而成的羟基磷灰石材料，其微观结构是由5～500nm的片状体、棒状体或丝状体自组装而成的0.1～5μm的中空微球。该缓释载体不仅具有优良的吸附和缓释性能，以及很好的化学稳定性，在人或动物体内不会产生排斥反应，也无毒副作用。而且原料来源广泛、都是可再生资源，不破坏生态环境，还能废物利用。生产方法简单。
The invention is a slow-release carrier with nanometer structure for medicine, which relates to a carrier material with medicine slow-release effect. The carrier is a hydroxyapatite material modified from mollusc hard tissue with calcium carbonate and aragonite structure. Its microstructure is self-assembled by 5-500nm flakes, rods or filaments. 0.1-5 μm hollow microspheres. The slow-release carrier not only has excellent adsorption and slow-release properties, but also good chemical stability, and will not produce rejection reaction in human or animal body, and has no toxic and side effects. Moreover, the raw materials come from a wide range of renewable resources, do not damage the ecological environment, and can also be used for waste utilization. The production method is simple.
Description
Technical field:
The present invention relates to have the carrier material of medicament slow release effect.
Background technology:
Common discontinuity administering mode, make the intravital drug level of people can only keep the short time, drug level in the blood or in the in-vivo tissue fluctuates bigger up and down, often surpass the medicine maximum tolerated dose or be lower than most effective dose, so not only do not have due curative effect, but also may have side effects.Frequent low dose of administration can be regulated blood drug level, but this makes the patient be difficult to accept, and has implemented a lot of difficulties.Therefore, the slow-releasing prolonged action drug that preparation can slowly discharge ingredient is in demand, and this key wherein is the carrier material that preparation can make the drug slow release of being carried.Invented multiple slow-release material now, for example, with poly butyric ester parcel stable [Chen Jianhai, Chen Zhiliang, Hou Lianbing.The functional polymer journal, 2000,113 (1): 61], use chitosan as slow release body [Zhang Ying, Hou Chunlin, Chen Aimin, Bao Jianzhong.China's experimental surgery magazine, 2000,17 (2): 132] etc.But, because types of drugs is various, numerous and jumbled, the requirement of slow-released carrier being had nothing in common with each other, the demand of therefore developing the slow releasing carrier of medication material of new capability, new component or new construction is very large.
Summary of the invention:
The purpose of this invention is to provide a kind of new slow-released carrier that can be used for medicine with nanostructured.
Solution of the present invention is as follows:
This carrier is the hydroxyapatite material that is formed by molluscan sclerous tissues's modification with calcium carbonate composition and aragonite structure, and its microstructure is the hollow microsphere of 0.1～5 μ m that formed by the plates of 5～500nm, clava or filamentous self assembly.
In such scheme, described carrier also can contain the carbonate smaller or equal to 10% weight ratio.
In such scheme, described molluscan sclerous tissues with calcium carbonate composition and aragonite structure is Endoconcha Sepiae, shell or Margarita.
The present invention be with Mollusca on one's body with the sclerous tissues with calcium carbonate composition and aragonite structure---comprise process hydro-thermal reactions such as the shells (abbreviation shell) of Endoconcha Sepiae, various shellfishes and Margarita and modification becomes hydroxyapatite.
Provide the chemical equation of this class hydro-thermal reaction of example below
This hydro-thermal reaction must be carried out the sufficiently long time, makes the hydroxyapatite of generation become the hollow microsphere of 0.1～5 μ m that hydroxyapatite plates, clava or filamentous self assembly by 5～500nm size (being nano-grade size) form.That is this hydroxyapatite has the hollow microsphere of nanostructured: there are a large amount of nano-grade body, clava or filamentous (but their self assemblies and form microsphere) in microsphere inside, and the duct of the connection of a large amount of nano-scales is contained in microsphere inside simultaneously.The hydroxyapatite of this nanostructured is compared with common hydroxyapatite has special performances, thereby it can be used as slow-released carrier.This is because plates, clava or the filamentous of the inner a large amount of nano-grade sizes that exist of microsphere have greatly increased its specific surface area and chemical-biological activities, can play great function for the slow release of medicine.At first, nanometer sheet, rod, silk all have very big specific surface, thereby very strong absorption and bearing capacity are arranged, and this makes each microsphere can become a little and capacious drug depot of size.The second, there is the duct of the connection of a large amount of nano-grade sizes in microsphere inside, and this can be discharged the medicine that adsorbs in the microsphere with regard to being provided a large amount of passages by medicament-carried release continuously; And the nano-scale in duct has guaranteed the slow of rate of release.Simultaneously, nanometer hydroxyapatite sheet, rod, silk can make also that to the strong adsorption of medicine rate of release is slow.
On the other hand, this hydroxyapatite micro-sphere also is foolproof as slow releasing carrier of medication.Because the chemical formula of hydroxyapatite is Ca
10(PO
4)
6(OH)
2, identical with human or animal's skeleton, tooth composition, in human or animal body, can not produce rejection, also have no side effect, and do not dissolved by gastro-intestinal Fluid, after discharging medicine, can all discharge with feces.Simultaneously, the chemical stability of hydroxyapatite is fine, and to many medicines chemically reactive not, the slow-released carrier that can be used as multiple medicine uses.
Molluscan sclerous tissues's wide material sources of the present invention with calcium carbonate composition and aragonite structure, for example Endoconcha Sepiae, Margarita, the shell (shell that comprises various sea water, fresh water and land shellfish, as clam shell, mussel shell, mussel shell, snail shell, Crusta Limax etc.), they all are Renewable resources, wherein the overwhelming majority still is garbage in daily life, they are utilized not only do not destroy ecological environment, can also twice laid, environment purification.
The preparation process of slow-released carrier proposed by the invention is as follows: after at first these natural materials (its composition is a calcium carbonate) will being cleaned, in boiled water, boiled 2 hours or in the weak solution of NaOCl (about 5%) soaked 30 minutes, to remove organic matter wherein.Then these raw materials are cleaned with distilled water.Secondly, treated raw material is fully immersed in concentration greater than in 6% the aqueous phosphatic, phosphatic amount is greater than and equals the amount that needs in the chemical equation [1].Be placed on then and carry out hydro-thermal reaction in the autoclave.Hydro-thermal reaction will (be carried out under 1～6000atm) in uniform temperature (100～600 ℃) and certain pressure; Employed phosphate kind there is not special restriction, for example: K
3PO
4, Na
3PO
4, (NH
4)
3PO
4, (NH
4)
2HPO
4, (NH
4) H
2PO
4, Li
3PO
4, LiH
2PO
4, Na
2HPO
4, NaH
2PO
4, Na
3H
3(PO
4)
2, Na
4H
5(PO
4)
3, NaH
5(PO
4)
2, KH
2PO
4, KH
5(PO
4)
2, NH
4H
5(PO
4)
3, 2CaOP
2O
5, CaOP
2O
5, CaHPO
4, Ca
4P
2O
9, Ca (H
2PO
4)
2Deng all using.The acid-base value of reaction can be adjusted in pH value is 6～10 scope according to the phosphate kind.The time of reaction is wanted long enough, can carry out in 0.5 hour～20 days time under different condition fully, up to by calcium carbonate modified and its microstructure of hydroxyapatite that generate has become the hollow microsphere of nanostructured.Specifically temperature, pressure, raw material properties, phosphatic kind and the concentration of time length visual response is different and different, can determine the suitable time by routine test.
Want realization response complete, must guarantee to add by above-mentioned chemical equation the phosphate of capacity, promptly raw material is 10: 6 with the ratio of phosphatic mole.Certainly, it is highly effective using excessive phosphate that accelerated reaction process and assurance are reacted completely.
Reaction finishes, and product is cleaned up with distilled water, promptly obtains having the aggregation (accompanying drawing showed by the Endoconcha Sepiae modification the form of hydroxyapatite hollow microsphere under scanning electron microscope of nanostructured) of the hydroxyapatite hollow microsphere of nanostructured.This aggregation is required slow-released carrier product, can be processed into bulk, granular or powdery etc. as required.Our experiments show that this aggregation all has good slow releasing function to antiepileptic lithium carbonate, downern magnesium sulfate etc.
If in modifying process, fail fully with the calcium carbonate conversion, make calcium carbonate or other carbonate that still has a little in the aggregation of hydroxyapatite hollow microsphere, as long as its weight ratio shared in product population is not more than 10%, then application can not exert an influence as slow-released carrier to this product.
In sum, the present invention is a kind of brand-new, carrier that can be used for medicament slow release with nanostructured.This slow-released carrier not only has good absorption and sustained release performance, and good chemical stability, and raw material sources are extensive, production method is simple.Thereby good application prospect arranged.
Because specific surface is big especially, this product also can be used as the catalyst of chemical reaction, biological respinse or the carrier of catalyst.
Description of drawings:
Accompanying drawing 1 is the Endoconcha Sepiae (amplifying 200 times) before the modification, the visible significantly block aragonite of mm size.
Accompanying drawing 2 is the Endoconcha Sepiae (amplifying 350 times) after the modification, the visible significantly hydroxyapatite micro-sphere aggregation of micron-scale.
Accompanying drawing 3 is the Endoconcha Sepiae (amplifying 10000 times) after the modification, the nanostructured of visible hydroxyapatite micro-sphere.
The specific embodiment:
Embodiments of the invention are as follows:
Embodiment 1 Endoconcha Sepiae is after cleaning treatment, and at 80 ℃, 1 atmospheric pressure, pH value are under 10 the condition, is 30% (NH in concentration
4)
2HPO
4Reaction is 21 days in the aqueous solution, can obtain the hydroxyapatite hollow microsphere of nanostructured.
Embodiment 2 Endoconcha Sepiaes are after cleaning treatment, and at 180 ℃, 10 atmospheric pressure, pH value are under 8 the condition, are 25% (NH in concentration
4)
2HPO
4Reaction is 8 days in the aqueous solution, can obtain the hydroxyapatite hollow microsphere of nanostructured.
The shell of embodiment 3 mussels is after cleaning treatment, and at 200 ℃, 13 atmospheric pressure, pH value are under 9 the condition, is 10% (NH in concentration
4)
3PO
4Reaction is 9 days in the aqueous solution, can obtain the hydroxyapatite hollow microsphere of nanostructured.
The shell of embodiment 4 mussels is after cleaning treatment, and at 250 ℃, 1600 atmospheric pressure, pH value are under 6 the condition, is 15% (NH in concentration
4) H
2PO
4Reaction is 3 days in the aqueous solution, can obtain the hydroxyapatite hollow microsphere of nanostructured.
Embodiment 5 Margaritas are after cleaning treatment, and at 130 ℃, 4 atmospheric pressure, pH value are under 10 the condition, are 10% NaH in concentration
2PO
4Reaction is 8 days in the aqueous solution, can obtain the hydroxyapatite hollow microsphere of nanostructured.
Claims (5)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB011340827A CN1187092C (en) | 2001-10-22 | 2001-10-22 | Slow-released carrier with nano structure for drug |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB011340827A CN1187092C (en) | 2001-10-22 | 2001-10-22 | Slow-released carrier with nano structure for drug |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1413735A CN1413735A (en) | 2003-04-30 |
| CN1187092C true CN1187092C (en) | 2005-02-02 |
Family
ID=4672217
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB011340827A Expired - Fee Related CN1187092C (en) | 2001-10-22 | 2001-10-22 | Slow-released carrier with nano structure for drug |
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| CN (1) | CN1187092C (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100334036C (en) * | 2004-07-14 | 2007-08-29 | 天津大学 | Composite microsphere containing hydroxyapatite and preparing method thereof |
| CN101983728B (en) * | 2010-11-09 | 2013-12-04 | 厦门大学 | Shell porous hydroxyapatite basal bone repair material and preparation method thereof |
| CN102674285A (en) * | 2012-05-14 | 2012-09-19 | 上海师范大学 | Preparation method of hollow carbonate radical type hydroxyapatite |
| FR3037801B1 (en) * | 2015-06-23 | 2017-08-11 | Jd Invest | PULVERULENT SEMI-SYNTHETIC MATERIAL, OBTAINED BY MODIFICATION OF THE COMPOSITION OF A NATURAL MARINE BIOMATERIAL, ITS MANUFACTURING PROCESS, ITS APPLICATIONS |
| CN109329794B (en) * | 2018-11-02 | 2022-04-19 | 江西省农业科学院 | Fishbone nano material and preparation and application thereof |
| CN109835878B (en) * | 2019-04-08 | 2020-08-18 | 山东大学 | Hydroxyapatite nano-column self-assembly microsphere and preparation method thereof |
-
2001
- 2001-10-22 CN CNB011340827A patent/CN1187092C/en not_active Expired - Fee Related
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