CN109701031A - The application and method of a kind of cucurbit(7)uril in adefovirdipivoxil sustained release - Google Patents
The application and method of a kind of cucurbit(7)uril in adefovirdipivoxil sustained release Download PDFInfo
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- CN109701031A CN109701031A CN201811535167.2A CN201811535167A CN109701031A CN 109701031 A CN109701031 A CN 109701031A CN 201811535167 A CN201811535167 A CN 201811535167A CN 109701031 A CN109701031 A CN 109701031A
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- cucurbit
- adefovirdipivoxil
- uril
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Abstract
The application and method that the invention discloses a kind of cucurbit(7)urils in adefovirdipivoxil sustained release, method are that super molecule inclusion compound is made using cucurbit(7)uril and adefovirdipivoxil as raw material.The present invention has expanded the application of cucurbit(7)uril, is of great significance to the sustained release of adefovirdipivoxil drug.
Description
Technical field
Application and method the present invention relates to a kind of cucurbit(7)uril, especially a kind of cucurbit(7)uril is in adefovirdipivoxil sustained release
Application and method.
Background technique
Melon ring (Cucurbit [n] uril), also known as Cucurbituril, (abbreviation CB [n] or Q [n] are obtained because structure is similar to pumpkin
Name, is the novel caged host compound of another class after the macrocyclic compound such as crown ether, cyclodextrin, calixarenes.From structural
From the point of view of, there is melon ring a hydrophobic cavity and both ends to be covered with polar carbonylic oxygen atom, this this structure is conducive to
Melon ring utilizes electrostatic force under solution state, hydrogen bond, hydrophobic effect, and π-π is stacked or the interactions selectivity such as electric charge transfer
The suitable small organic molecule of inclusion size, large biological molecule or with occur at port with dipole or ionic compound it is hydrophilic
Property coordination；It functionally sees, due to the particularity and the associativity excellent with guest molecule of melon ring structure, melon ring is in medicine
Object transport, Controlled release and increase medicine stability etc. are of great significance.
Cucurbit(7)uril (Cucurbit [7] urils) also known as cucurbit [7] urea, be by glycosides urea unit by methylene-bridged
The big ring cage compound with special hydrophobicity cage body and hydrophily port come.
Adefovirdipivoxil can mix viral DNA chain with adenylate competitiveness, and the termination object as DNA chain inhibits archaeal dna polymerase,
The synthesis of DNA chain is terminated, and is suppressed the duplication of virus, endogenous alpha-interferon can also be induced, increases natural kill
The immune response of the vigor and stimulation body of cell (NK), there is stronger AntiHIV1 RT activity, HBV and herpesviral.It was found that application
Adefovir treatment hepatitis B finds the removing of HBV in Bipolar.
Summary of the invention
The application and method that the object of the present invention is to provide a kind of cucurbit(7)urils in adefovirdipivoxil sustained release.The present invention
The application for having expanded cucurbit(7)uril is of great significance to the sustained release of adefovirdipivoxil drug.
A kind of technical solution of the present invention: the application of cucurbit(7)uril in adefovirdipivoxil sustained release.
A kind of method of the application of cucurbit(7)uril above-mentioned in adefovirdipivoxil sustained release, is with cucurbit(7)uril and adefovirdipivoxil
Super molecule inclusion compound is made as raw material.
The method of application of the cucurbit(7)uril above-mentioned in adefovirdipivoxil sustained release, the molecular formula of the super molecule inclusion compound are
C50H54N33O18P, structural formula are as shown in Fig. 1.
The method of application of the cucurbit(7)uril above-mentioned in adefovirdipivoxil sustained release, the preparation method of the super molecule inclusion compound
It is that cucurbit(7)uril and adefovirdipivoxil are added in distilled water to be hybridly prepared into mixed solution, 35-50 DEG C is then heated to, until anti-
It should cool down afterwards completely to get cucurbit(7)uril-adefovirdipivoxil supermolecule medicinal inclusion compound.
The method of application of the cucurbit(7)uril above-mentioned in adefovirdipivoxil sustained release, the specific steps are as follows:
1) ratio by cucurbit(7)uril and adefovirdipivoxil according to molar ratio greater than 1:1 mixes, and distilled water is then added and prepares
At mixed solution, A product are obtained；
2) A product are heated up to 35-50 DEG C while stirring, reacts 1-3 hours, obtains B product；
3) B product are cooled to room temperature until obtaining colourless transparent solution to get cucurbit(7)uril-adefovirdipivoxil supermolecule drug
Inclusion compound.
The method of application of the cucurbit(7)uril above-mentioned in adefovirdipivoxil sustained release, the cucurbit(7)uril and adefovirdipivoxil according to
The ratio of molar ratio 1:1 mixes.
The method of application of the cucurbit(7)uril above-mentioned in adefovirdipivoxil sustained release, in the A product, cucurbit(7)uril and A Defu
The concentration of Wei is 1.0 × 10-4mol·L-1。
The method of application of the cucurbit(7)uril above-mentioned in adefovirdipivoxil sustained release, in the step 2), warm temperature 40
DEG C, reaction time 2h.
Beneficial effects of the present invention
1, cucurbit(7)uril is used for the Controlled release of adefovirdipivoxil by the present invention, extends the application of cucurbit(7)uril.
2, the supermolecule medicinal inclusion compound tool good water solubility and knot that cucurbit(7)uril of the present invention and adefovirdipivoxil are constructed
The stable feature of structure, this is of great significance to application of the promotion melon ring in terms of pharmaceutical chemistry.
The supermolecule drug inclusion complex and drug adefovirdipivoxil of the application is respectively put into bag filter the pH=1.2 the case where
Imitating simulated gastric fluid does external sustained release, and drug adefovirdipivoxil released completely at 35 minutes, and adefovirdipivoxil and cucurbit(7)uril
Inclusion complex is sustained in vitro to be released completely at 85 minutes.Simulated intestinal fluid is simulated in the case where pH=6.8 does external sustained release, drug
Adefovirdipivoxil released completely at 25 minutes, and adefovirdipivoxil and cucurbit(7)uril inclusion complex are sustained released completely at 145 minutes in vitro
It discharges.Supermolecule drug inclusion complex, which has, obviously slows down rate of release, reduces drug to the toxicity of human body.
Detailed description of the invention
Attached drawing 1 is the structural schematic diagram of inclusion compound of the invention；
Attached drawing 2 is the structure chart of guest molecule adefovirdipivoxil (ADV) and Q [7]；
Attached drawing 3 is cucurbit(7)uril Q [7] and the 1H NMR titration figure (500MHz, D2O) of adefovirdipivoxil；
Attached drawing 4 is the isothermal titration calorimetric figure of cucurbit(7)uril Q [7] and adefovirdipivoxil；
Attached drawing 5 is the ultraviolet emission spectrum change spectrogram of cucurbit(7)uril Q [7] and adefovirdipivoxil；
Attached drawing 6 is in vitro drug release ultraviolet spectra spectrogram.
Specific embodiment
Below with reference to embodiment, the present invention is further illustrated, but is not intended as the foundation limited the present invention.
The embodiment of the present invention
Embodiment 1: a kind of method of the application of cucurbit(7)uril in adefovirdipivoxil sustained release, is by cucurbit(7)uril and A Defu
Super molecule inclusion compound is made in Wei Zuowei raw material, the preparation method is as follows:
1) cucurbit(7)uril and adefovirdipivoxil are mixed according to the ratio of molar ratio 1:1, distilled water is then added and is configured to seven
The concentration of first melon ring and adefovirdipivoxil is 1.0 × 10-4mol·L-1Mixed solution, obtain A product；
2) A product are heated up to 40 DEG C while stirring, reacts 2 hours, obtains B product；
3) B product are cooled to room temperature until obtaining colourless transparent solution to get cucurbit(7)uril-adefovirdipivoxil supermolecule drug
Inclusion compound.
Embodiment 2: a kind of method of the application of cucurbit(7)uril in adefovirdipivoxil sustained release, is by cucurbit(7)uril and A Defu
Super molecule inclusion compound is made in Wei Zuowei raw material, the preparation method is as follows:
1) cucurbit(7)uril and adefovirdipivoxil are mixed according to the ratio of molar ratio 1.2:1, distilled water is then added and is configured to
The concentration of cucurbit(7)uril and adefovirdipivoxil is 1.0 × 10-4mol·L-1Mixed solution, obtain A product；
2) A product are heated up to 35 DEG C while stirring, reacts 1 hour, obtains B product；
3) B product are cooled to room temperature until obtaining colourless transparent solution to get cucurbit(7)uril-adefovirdipivoxil supermolecule drug
Inclusion compound.
Embodiment 3: a kind of method of the application of cucurbit(7)uril in adefovirdipivoxil sustained release, is by cucurbit(7)uril and A Defu
Super molecule inclusion compound is made in Wei Zuowei raw material, the preparation method is as follows:
1) cucurbit(7)uril and adefovirdipivoxil are mixed according to the ratio of molar ratio 1.5:1, distilled water is then added and is configured to
The concentration of cucurbit(7)uril and adefovirdipivoxil is 1.0 × 10-4mol·L-1Mixed solution, obtain A product；
2) A product are heated up to 38 DEG C while stirring, reacts 1.5 hours, obtains B product；
3) B product are cooled to room temperature until obtaining colourless transparent solution to get cucurbit(7)uril-adefovirdipivoxil supermolecule drug
Inclusion compound.
Embodiment 4: a kind of method of the application of cucurbit(7)uril in adefovirdipivoxil sustained release, is by cucurbit(7)uril and A Defu
Super molecule inclusion compound is made in Wei Zuowei raw material, the preparation method is as follows:
1) cucurbit(7)uril and adefovirdipivoxil are mixed according to the ratio of molar ratio 1.8:1, distilled water is then added and is configured to
The concentration of cucurbit(7)uril and adefovirdipivoxil is 1.0 × 10-4mol·L-1Mixed solution, obtain A product；
2) A product are heated up to 45 DEG C while stirring, reacts 2.5 hours, obtains B product；
3) B product are cooled to room temperature until obtaining colourless transparent solution to get cucurbit(7)uril-adefovirdipivoxil supermolecule drug
Inclusion compound.
Embodiment 5: a kind of method of the application of cucurbit(7)uril in adefovirdipivoxil sustained release, is by cucurbit(7)uril and A Defu
Super molecule inclusion compound is made in Wei Zuowei raw material, the preparation method is as follows:
1) cucurbit(7)uril and adefovirdipivoxil are mixed according to the ratio of molar ratio 2:1, distilled water is then added and is configured to seven
The concentration of first melon ring and adefovirdipivoxil is 1.0 × 10-4mol·L-1Mixed solution, obtain A product；
2) A product are heated up to 50 DEG C while stirring, reacts 3 hours, obtains B product；
3) B product are cooled to room temperature until obtaining colourless transparent solution to get cucurbit(7)uril-adefovirdipivoxil supermolecule drug
Inclusion compound.
Claims (8)
1. a kind of application of cucurbit(7)uril in adefovirdipivoxil sustained release.
2. a kind of method of application of cucurbit(7)uril according to claim 1 in adefovirdipivoxil sustained release, it is characterised in that:
It is that super molecule inclusion compound is made using cucurbit(7)uril and adefovirdipivoxil as raw material.
3. the method for application of the cucurbit(7)uril according to claim 2 in adefovirdipivoxil sustained release, it is characterised in that: described
The molecular formula of super molecule inclusion compound is C50H54N33O18P, structural formula are as follows:
4. the method for application of the cucurbit(7)uril according to claim 2 in adefovirdipivoxil sustained release, it is characterised in that: described
The preparation method of super molecule inclusion compound is that cucurbit(7)uril and adefovirdipivoxil are added in secondary water to be hybridly prepared into mixed solution, so
After be heated to 35-50 DEG C, cool down afterwards until the reaction is complete to get cucurbit(7)uril-adefovirdipivoxil supermolecule medicinal inclusion compound.
5. the method for application of the cucurbit(7)uril according to claim 4 in adefovirdipivoxil sustained release, it is characterised in that: specific
Steps are as follows:
1) ratio by cucurbit(7)uril and adefovirdipivoxil according to molar ratio greater than 1:1 mixes, and distilled water is then added and is configured to mix
Solution is closed, A product are obtained；
2) A product are heated up to 35-50 DEG C while stirring, reacts 1-3 hours, obtains B product；
3) B product are cooled to room temperature until obtaining colourless transparent solution and are included to get cucurbit(7)uril-adefovirdipivoxil supermolecule drug
Object.
6. the method for application of the cucurbit(7)uril according to claim 5 in adefovirdipivoxil sustained release, it is characterised in that: described
Cucurbit(7)uril and adefovirdipivoxil are mixed according to the ratio of molar ratio 1:1.
7. the method for application of the cucurbit(7)uril according to claim 5 in adefovirdipivoxil sustained release, it is characterised in that: described
In A product, the concentration of cucurbit(7)uril and adefovirdipivoxil is 1.0 × 10-4mol·L-1。
8. the method for application of the cucurbit(7)uril according to claim 5 in adefovirdipivoxil sustained release, it is characterised in that: described
In step 2), warm temperature is 40 DEG C, reaction time 2h.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811535167.2A CN109701031A (en) | 2018-12-14 | 2018-12-14 | The application and method of a kind of cucurbit(7)uril in adefovirdipivoxil sustained release |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811535167.2A CN109701031A (en) | 2018-12-14 | 2018-12-14 | The application and method of a kind of cucurbit(7)uril in adefovirdipivoxil sustained release |
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Family
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| CN201811535167.2A Pending CN109701031A (en) | 2018-12-14 | 2018-12-14 | The application and method of a kind of cucurbit(7)uril in adefovirdipivoxil sustained release |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100016610A1 (en) * | 2007-02-06 | 2010-01-21 | Technion Research & Development Foundation Ltd. | Frictionless molecular rotary motors |
| EP1644379B1 (en) * | 2003-07-05 | 2013-09-11 | Postech Foundation | Rotaxane compound, rotaxane-bonded solid substrate, and biochip using the same |
| CN108079313A (en) * | 2017-12-25 | 2018-05-29 | 贵州大学 | A kind of preparation method of cucurbit(7)uril and capecitabine super molecule inclusion compound |
-
2018
- 2018-12-14 CN CN201811535167.2A patent/CN109701031A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1644379B1 (en) * | 2003-07-05 | 2013-09-11 | Postech Foundation | Rotaxane compound, rotaxane-bonded solid substrate, and biochip using the same |
| US20100016610A1 (en) * | 2007-02-06 | 2010-01-21 | Technion Research & Development Foundation Ltd. | Frictionless molecular rotary motors |
| CN108079313A (en) * | 2017-12-25 | 2018-05-29 | 贵州大学 | A kind of preparation method of cucurbit(7)uril and capecitabine super molecule inclusion compound |
Non-Patent Citations (1)
| Title |
|---|
| 胡清华等: ""阿德福韦与七元瓜环超分子相互作用的研究"", 《山地农业生物学报》 * |
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Application publication date: 20190503 |