Patent Application
20180355102
Some references, which may include patents, patent applications and various publications, may be cited and discussed in the description of this disclosure. The citation and/or discussion of such references is provided merely to clarify the description of the present disclosure and is not an admission that any such reference is “prior art” to the disclosure described herein. All references cited and discussed in this specification are incorporated herein by reference in their entireties and to the same extent as if each reference was individually incorporated by reference.
The instant disclosure relates to a method for preparing a biomedical material, and more particularly to a method for preparing a biodegradable polyester elastomer having excellent biocompatibility and biodegradability and good mechanical properties.
In recent years, the incidence of ischaemic vascular diseases has increased year by year due to bad eating habits and aging population. In addition, cerebral, cardiac, or peripheral vascular disease caused by artery ischemia seriously affects human health, and thereby has more readily attracted the attention of doctors and researchers. Methods of clinical treatment for ischaemic diseases include targeting drugs, cavity intervention, vascular bridges, etc. However, these methods have the following problems: (1) the need for secondary surgery due to postoperative vascular occlusion; (2) the lack of biological compatibility and mechanical properties of intervention materials; and (3) the lack of stability and therapeutic effect of drugs. Hence, there is a need for methods of promoting vascularization of ischaemic tissue to effectively recover blood supply.
Vascular tissue engineering is one of the most effective ways to solve the aforementioned problems, and how to choose the best tissue engineering scaffold material is the key point thereof. In general, a suitable tissue engineering scaffold material should have the advantages of high specific surface area, good channel connectivity, high biological compatibility, adjustable degradation rate, good mechanical properties, and environmental benefits of cell culture and tissue growth. A material with high biological compatibility usually means that said material is a low toxicity non-carcinogenic material, and cannot cause any allergic reaction, thrombolysis, tissue multiplication, and infection.
Since tissue engineering scaffold materials with the characteristics of mechanical stimulation and biodegradability are beneficial to vascularization of ischaemic tissue, biodegradable elastomers are widely used in the field of biomedical materials. Biodegradable elastomers can be thermoplastic and thermoset. The thermoplastic elastomer is a block polymer which includes soft segments and hard segments interacting with the soft segments, and the thermoset elastomer is a star-branched polymer. Yadong Wang et al. disclose a melt-polymerization reaction between sebacic and glycerol (1:1 molar ration) for the production of poly(glycerol sebacate) (PGS). However, said melt-polymerization reaction will not only result in bad physical performance, but also take 24 hours or more. There is an urgent need for technologies used to improve the reaction rate and product yields of polymerization of biodegradable elastomers.
In response to the above-referenced technical inadequacies, the present disclosure provides a method for preparing a biodegradable polyester elastomer in a highly efficient manner. The biodegradable polyester elastomer can be produced within a relatively short period of time and has good comprehensive performance.
In one aspect, the present disclosure provides a method for preparing a biodegradable polyester elastomer, characterized in that it comprises a step of carrying out an esterification reaction between a diacid having 6 to 12 carbon atoms and glycerol in a molar ratio of 1:1-2 with an effective amount of sulfated titania under a vacuum pressure of 300-600 mTorr to produce a prepolymer.
In certain embodiments, the effective amount of the sulfated titania is at least 1.72 mol % based on the diacid and glycerol.
In certain embodiments, the diacid is sebacic acid, maleic acid, or adipic acid.
In certain embodiments, the esterification reaction is carried out at a temperature of 25-150° C.
In certain embodiments, the esterification reaction is carried out with a stirring speed of 300-400 rpm.
In certain embodiments, the sulfated titania is prepared by the steps of:dissolving a predetermined amount of titanium dioxide in an aqueous mixture of sulphuric acid, DI water, and ethanol to form a first solution; refluxing the first solution at a temperature of 90-100° C. and 1 atm to form a second solution; drying the second solution to form a catalyst raw material; and grinding the catalyst raw material and calcining resulting particles at a temperature of 350-550° C.
In certain embodiments, the second solution is dried at a temperature of 110° C.
In certain embodiments, the first solution is refluxed in a silicone oil bath with a stirring speed of 300-450 rpm.
In certain embodiments, the sulfated titania is a 500° C. calcined finished sulfated titania.
One of the advantages of the instant disclosure is that the method uses a sulfated solid catalyst to promote the esterification reaction between an acid compound and an alcohol compound, preferably between a diacid and glycerol, so that the reaction time can be reduced to less than about 60 minutes and the polyester elastomer (i.e., PGS polymer) produced has excellent biocompatibility and biodegradability and good mechanical properties.
These and other aspects of the present disclosure will become apparent from the following description of the embodiment taken in conjunction with the following drawings and their captions, although variations and modifications therein may be affected without departing from the spirit and scope of the novel concepts of the disclosure.
The present disclosure will become more fully understood from the detailed description and the accompanying drawings, in which:
The present disclosure is more particularly described in the following examples that are intended as illustrative only since numerous modifications and variations therein will be apparent to those skilled in the art. Like numbers in the drawings indicate like components throughout the views. As used in the description herein and throughout the claims that follow, unless the context clearly dictates otherwise, the meaning of “a”, “an”, and “the” includes plural reference, and the meaning of “in” includes “in” and “on”. Titles or subtitles can be used herein for the convenience of a reader, which shall have no influence on the scope of the present disclosure.
The terms used herein generally have their ordinary meanings in the art. In the case of conflict, the present document, including any definitions given herein, will prevail. The same thing can be expressed in more than one way. Alternative language and synonyms can be used for any term(s) discussed herein, and no special significance is to be placed upon whether a term is elaborated or discussed herein. A recital of one or more synonyms does not exclude the use of other synonyms. The use of examples anywhere in this specification including examples of any terms is illustrative only, and in no way limits the scope and meaning of the present disclosure or of any exemplified term. Likewise, the present disclosure is not limited to various embodiments given herein. Numbering terms such as “first”, “second” or “third” can be used to describe various components, signals or the like, which are for distinguishing one component/signal from another one only, and are not intended to, nor should be construed to impose any substantive limitations on the components, signals or the like.
Biodegradable elastomers can experience mechanical forces and deformation, and do not appear to affect surrounding tissues during the process of recovery. In addition, biodegradable elastomers have a certain water absorption ratio, high hydrophilicity, and mechanical properties that are similar to proteins. Accordingly, they can be applied in biomedical field to be used as templates for forming tissue engineering scaffold materials. The present disclosure provides a method for preparing a biodegradable polyester elastomer that is a prepolymer produced with a superacid catalyst under specific reaction conditions (e.g., temperature, pressure and vacuum degree). Therefore, the production time of the biodegradable polyester elastomer can be reduced to less than about 60 minutes so as to meet the requirements of large-scale production. In addition, the superacid catalyst can be recovered from the prepolymer for reuse.
Referring to
It is worth mentioning that the method use a superacid catalyst to promote the esterification reaction between an acid compound and an alcohol compound, preferably between a diacid and glycerol, so that the reaction time can be reduced significantly. The biodegradable polyester elastomer prepared is a prepolymer and has good comprehensive performance, thereby being widely used in biomedical fields as well as industrial fields.
In the step S100, the acid compound and the alcohol compound can be mixed in a reactor. In the present embodiment, the acid compound is a diacid having 6 to 12 carbon atoms and the alcohol compound is glycerol, and the molar ratio between the diacid and glycerol is 1:1-2. The diacid is preferably sebacic acid, maleic acid, or adipic acid. The reactor can be a batch reactor, but is not limited thereto. In practice, any suitable reactor well known in the art can be used to mix the acid compound and the alcohol compound.
In other embodiments, the acid compound can be a polybasic acid having more than 6 carbon atoms. Specific examples of the polybasic acid include suberic acid, azelaic acid, citric acid, phthalic acid, isophthalic acid, trimellitic acid, and 1,2,4,5-pyromellitic acid. The alcohol compound can be a polyol having 4 to 10 carbon atoms. Specific examples of the polyhydric alcohol include ethylene glycol, 1,2-propylene glycol, 1,3-propane diol, glycerol, 1,4-butane diol, 1,3-butane diol, 1,6-hexane diol, 1,10-decane diol, diethylene glycol, triethylene glycol, pentaerythritol, and pentaerythritol.
In the step S102, the superacid catalyst being involved in the esterification reaction is added to the mixture of the acid compound and the alcohol compound in solid form. The preferable reaction conditions include a reaction temperature of 25-150° C., a vacuum pressure of 300-600 mTorrs, and a stirring speed of 300-400 rpm. Accordingly, the reaction time can be reduced to less than about 60 minutes. The biodegradable polyester elastomer prepared is preferably a glycerol-sebacic acid (poly(glycerol sebacate)) prepolymer, a glycerol-maleic acid prepolymer, or a glycerol-adipic acid (poly(glycerol adipate)) prepolymer, but is not limited thereto.
More specifically, the superacid catalyst can be a sulfated solid catalyst such as a sulfated metal oxide (SMO) represented by the formula (1) or (2), where M represents metal such as Zr, Ti, Sn, Hf, Fe, Al.
Specific examples of the superacid catalyst include sulfated titanium (TiO2/SO42−), sulfated zirconia (ZrO2/SO42−), sulfated stannia (SnO2/SO42−), sulfated hafnia (HfO2/SO42), sulfated stannia (Fe2O3/SO42−), sulfated iron oxide (Fe2O3/SO42−), andsulfated alumina (Al2O3/SO42−).
It is worth to note that the superacid catalyst has a tetragonal crystal structure and exhibits both Lewis and Bronsted acidity, so that it can promote the esterification reaction between an acid compound and an alcohol compound. The superacid catalyst has good stability and can be easily regenerated even at a relatively low temperature. In addition, the superacid catalyst can be easily prepared and is very suitable for being used in industrial reactions.
In the present embodiment, the superacid catalyst is sulfated titania that is present in an amount of at least 1.72 mol % based on the acid and alcohol compounds. The superacid catalyst is prepared by wet impregnation, so that sulfate ions can be uniformly bonded to the surface of titania. More specifically, a predetermined amount of titanium dioxide (TiO2) is dissolved in an aqueous mixture of sulphuric acid (H2SO4), DI water, and ethanol (C2H5OH) to form a first solution firstly. In practice, the titanium dioxide can be present in an amount of 0.125 mole, the sulphuric acid can be present in an amount of 0.5 mole, the DI water can be present in an amount of 5.5 mole, and the ethanol can be present in an amount of 2.17 mole. Next, the first solution is refluxed at a temperature of 90-100° C. and 1 atm to form a second solution. Next, the second solution is dried to form a catalyst raw material. Finally, the catalyst raw material is ground and the resulting particles are calcined at a temperature of 350-550° C. for at least four hours. It is worth mentioning that the 500° C. calcined finished sulfated titania is an optimized superacid catalyst for the esterification reaction.
Reference is made to
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Reference is made to
In the step S104, the semi-finished products formed in the step S102 are molded with a crosslinking agent to form a final product. The final product has excellent mechanical properties (e.g., tensile strength), wear resistance, solvent resistance, weather resistance, and gas tightness. In practice, any suitable molding mean well known in the art can be used to mold the semi-finished products.
One of the advantages of the instant disclosure is that the method use a sulfated solid catalyst to promote the esterification reaction between an acidic compound and an alcohol compound, preferably between sebacic acid and glycerol, so that the reaction time can be reduced to less than about 60 minutes and the polyester elastomer (i.e., PGS polymer) produced has excellent biocompatibility and biodegradability and good mechanical properties.
Based on the above, the method can meet the requirements of large-scale production, and the polyester elastomer can be widely used in biomedical fields as well as industrial fields.
In addition, the superacid catalyst can be recovered from the prepolymer for reuse, so that the method has environmental and economic benefits.
The foregoing description of the exemplary embodiments of the disclosure has been presented only for the purposes of illustration and description and is not intended to be exhaustive or to limit the disclosure to the precise forms disclosed. Many modifications and variations are possible in light of the above teaching.
The embodiments were chosen and described in order to explain the principles of the disclosure and their practical application so as to enable others skilled in the art to utilize the disclosure and various embodiments and with various modifications as are suited to the particular use contemplated. Alternative embodiments will become apparent to those skilled in the art to which the present disclosure pertains without departing from its spirit and scope.
| Number | Date | Country | Kind |
|---|---|---|---|
| 104143780 | Dec 2015 | TW | national |
This application is a continuation-in-part of U.S. application Ser. No. 15/154,263, filed on 13 May 2016 and entitled “TISSUE ENGINEERING SCAFFOLD MATERIAL AND BIODEGRADABLE POLYESTER ELASTOMER THEREOF”, now pending, the entire disclosures of which are incorporated herein by reference.
| Number | Date | Country | |
|---|---|---|---|
| Parent | 15154263 | May 2016 | US |
| Child | 16102787 | US |
