CN104211950A - Nonlinear polymer and preparation and use thereof - Google Patents
Nonlinear polymer and preparation and use thereof Download PDFInfo
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- CN104211950A CN104211950A CN201310218702.2A CN201310218702A CN104211950A CN 104211950 A CN104211950 A CN 104211950A CN 201310218702 A CN201310218702 A CN 201310218702A CN 104211950 A CN104211950 A CN 104211950A
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Abstract
The invention discloses a new nonlinear polymer containing a metal ion structure, and a preparation method and use thereof. A compound with a branch structure is used for construction of the new nonlinear polymer, and the new structure is used for testing in eczema animal models, and the new compound has excellent therapeutic effect on the treatment of eczema disease.
Description
Technical field
The invention discloses preparation method and the purposes of a kind of non-linear polymer and this polymkeric substance.
Background technology
Eczema has ear eczema, Hand and Foot Eczema, eczema mammae, anus eczema of external genitalia, legs eczema etc.Eczema can occur in any position, but take exsertion part and side in the wrong as common; Fash often symmetry distributes.Eczema has a variety of classification, and more common classification is by skin, to damage characteristicness to be divided into three kinds of acute, subacute and chronic eczemas.Wherein acute eczema is most grain grain large red papules, papulo-vesicle or blister, still has obvious point-like or strip rotten to the corn, sepage, incrustation.Infringement indefinite border.During concurrent infection, can occur that warts, purulence are oozed out and scab bits etc.; Subacute eczema is often dealt with improperly and is delayed to come because of acute phase infringement, and skin damages take red papule, maculopapule or incrustation as main, has minority papulo-vesicle or blister and rotten to the corn sepage concurrently; That chronic eczema has more is acute, subacute eczema is not more transformed repeatedly, and skin damages as dark red or reddish brown color spot or maculopapule, and permelting is closed to thicken and is lichenification, and there is scab etc. on surface, is dispersed in minority papule, maculopapule etc. around.With ointments such as glucocorticosteroid, zinc oxide, furoic acid momisones, treat clinically, but result for the treatment of is limited, efficient not high.The inventor is surprised to find that a kind of compound has an unexpected effect on the medicine of preparation treatment eczema, there is no report at present for this base polymer treatment eczema.
Summary of the invention
1. its structure is as follows:
A representation metal ion wherein, preferred calcium ion, magnesium ion, cobalt ion, barium ion, platinum ion, nickel ion, cupric ion.Wherein the molecular weight polyethylene glycol in polymkeric substance is 100-200000, the integer between m=1-5000, the preferably integer between m=1-2000.The preparation method of this compound, is characterized in that:
1) the structure A that contains nitrilotriacetic acid(NTA)-Methionin reacts and obtains Compound C with compd B in sodium hydrogen carbonate solution;
2) Compound C with containing obtaining compd E after the star-like compound D stirring reaction of polyoxyethylene glycol; Wherein the molecular weight polyethylene glycol in polymkeric substance is 100-200000;
3) compd E reacts to obtain compound F 17-hydroxy-corticosterone with metal ion compound;
Compd A;
Compd B;
Compound C;
Compound D, the integer between m=1-5000, the preferably integer between m=1-2000;
Compd E;
Reaction gained compound F 17-hydroxy-corticosterone, wherein A representation metal ion.Wherein said chemical step selects solvent to be selected from: one or more in acetic acid, formic acid, benzene, toluene, pyridine, tetrahydrofuran (THF), trifluoroacetic acid, chloroform, tetracol phenixin, methylene dichloride, methyl alcohol, ethanol, methylene dichloride, dimethyl sulfoxide (DMSO), DMF.
Wherein most preferred configuration is:
With
Integer between m=1-5000, the preferably integer between m=1-2000.
Wherein said chemical reaction step selects solvent to be selected from: one or more in acetic acid, formic acid, benzene, toluene, pyridine, tetrahydrofuran (THF), trifluoroacetic acid, chloroform, tetracol phenixin, methylene dichloride, methyl alcohol, ethanol, methylene dichloride, dimethyl sulfoxide (DMSO), DMF.Compound can be prepared into and be suitable for muscle, vein or the preparation of topical.Described preparation, it can be ordinary preparation, controlled release preparation, targeting preparation etc.Described part is percutaneous drug delivery or other mode administrations.Described compound and pharmacologically acceptable salt thereof the purposes in the medicine of preparation treatment eczema.Preparation method of the present invention is specific as follows:
Preparation method of the present invention is specific as follows:
By compd A (being purchased) 10mg-10g and compd B (being purchased) 0.01g-5g as for 0.1-96 hour in solvent, cooling after 1-48 hour in 50 degree-100 degree heating, regulate PH to 2-5, after concentrating under reduced pressure, in ethanol, wash, after dry, obtain Compound C, the star-like compound D(that contains polyoxyethylene glycol being purchased is purchased) in phosphoric acid salt, stir 1-10 hour with C, concentrating under reduced pressure obtains compd E, and compd E reacts 1-48 hour to obtain final product compound F 17-hydroxy-corticosterone with the metal ion compound of 1-5mol.Then directly use or make the freeze-dried preparation obtaining after related preparations freeze-drying.
Reaction scheme is:
Compd A
+
Compd B
Generate
Compound C;
Compound C
+
Compound D
Generate
Compd E;
Compd E
+
Metal ion compound
Generate
Compound F 17-hydroxy-corticosterone
This compound of preparing at this patent can be treated eczema in vivo, and effect is very good.
accompanying drawing explanation:
fig. 1the nuclear magnetic resonance map of preparing product of embodiment 1.
fig. 2the nuclear magnetic resonance map of preparing product of embodiment 2.
Embodiment
Specific embodiment is described in further detail the present invention below, but the present invention not only limits to following examples.
Preparation Example is as follows:
embodiment 1
Compd A (being purchased) 500mg is dissolved in 6ml water, with 600mg sodium bicarbonate and 500mg compd B (being purchased) as in same beaker 15 hours, cooling after heating 70 degree, acetic acid regulator solution PH to 3, after concentrating under reduced pressure, in ethanol, wash, crystallization obtains Compound C, filtering ethanol washs rear dry again, the star-like compound D(that 400mg contains polyoxyethylene glycol (molecular weight 10000) is purchased) be dissolved in the phosphoric acid buffer of PH7.5, add 2ml methyl alcohol, and stir 2 hours with Compound C, concentrating under reduced pressure, washing with alcohol, filter and wash again, vacuum-drying obtains compd E, the CoCl of compd E and 8Mol
2react to obtain compound F 17-hydroxy-corticosterone.
embodiment 2
Compd A (being purchased) 1000mg is dissolved in 6ml water, with 700mg sodium bicarbonate and 1100mg compd B (being purchased) as in same beaker 24 hours, cooling after heating 75 degree, acetic acid regulator solution PH to 3.3, after concentrating under reduced pressure, in ethanol, wash, crystallization obtains Compound C, filtering ethanol washs rear dry again, the star-like compound D(that 800mg contains polyoxyethylene glycol (molecular weight 2000) is purchased) be dissolved in the phosphoric acid buffer of PH7.3, add 3ml dimethyl sulfoxide (DMSO), and stir 2 hours with Compound C, concentrating under reduced pressure, washing with alcohol, filter and wash again, vacuum-drying obtains compd E, the MgCl of compd E and 8Mol
2deserved compound F 17-hydroxy-corticosterone in the aqueous solution of a small amount of methylene dichloride.
effect embodiment:
The therapeutic action of medicine to eczema
1, suppress swelling effect: 90 of rats, be divided at random 9 groups, every group 10, be divided at random 9 groups, normal group, model group, furoic acid momisone group, polyoxyethylene glycol group, metal ion group (muriate) and medicine embodiment group, experiment is when daily liquid capacity method, with homemade volume determination device, measure the right back sufficient volume of respectively organizing rat, smear medicine (medicine embodiment group then to each group, polyoxyethylene glycol group, it is 25ul that metal ion group (muriate) is coated with dose, concentration is 0.2mg/ml, the painting dose of furoic acid momisone group is 30mg/), wherein normal group and model group are smeared distilled water, after 1 hour, the egg white of the right back sufficient subcutaneous injection 10% of each group (except normal group) (every injection 0.05ml).Then with volumetric method, measure 1 hour, 2 hours, 4 hours, the right back sufficient volume of 6 hours, right back sufficient volume change value and just initial body machine are worth being relatively swelling rate, and the swelling rate after medication of each group is relatively evaluated the action effect of medicine embodiment.
Table 1 swelling rate test-results (n=10)
| Group | 4 hours swelling rates (%) | 6 hours swelling rates (%) |
| Normal group | 0.0±1.9** | 0.0±2.4** |
| Model group | 54.0±12.3 | 53.2±16.4 |
| Furoic acid momisone group | 47.0±9.8* | 44.0±14.3* |
| Polyoxyethylene glycol group | 52.7±8.7 | 55.3±10.3 |
| CoCl2 | 52.4±9.5 | 55.1±10.5 |
| MgCl2 | 50.2±9.7 | 56.0±11.3 |
| Embodiment 1 | 22.1±11.2** | 16.8±9.2** |
| Embodiment 2 | 22.3±11.5** | 16.7±9.3** |
Compare * P<0.05**P<0.01 with model group
2, itching-relieving action: cavy is divided into 9 groups at random, normal group, model group, furoic acid momisone group and medicine embodiment group, 10 every group.Test first 24 hours by each group Guinea Pig Left dorsal portion unhairing, the about 1cm of area
2, and carry out coating the 1st time, and the painting dose of medicine embodiment group, polyoxyethylene glycol group, metal ion group is 25ul, and concentration is 0.2mg/ml, and it is to smear twice that positive drug furoic acid momisone group is coated with dose 30mg/ every day.With flint paper, abrade unhairing place, left back instep, coating 1 time is coating again after 1 hour then, after administration 3 hours, only smears 0.01% histamine phosphate 0.05mL/ at cavy surface of a wound place, observe 5min, after this every 5min, use successively the concentration of 0.02%, 0.03%, 0.04% speed increase administration histamine phosphate, only be 50ul/ at every turn, until occur that cavy later licks left back foot, the cumulative histamine phosphate total amount of giving is itch-threshold, record relatively each treated animal itch-threshold.
The impact (n=10) of table 2 medicine on guinea pig skin itch due to histamine phosphate
| Group | Itch-threshold (histamine phosphate total amount mg) |
| Normal group | 530.6±28.0** |
| Model group | 110.2±29.6 |
| Furoic acid momisone group | 221.0±37.3* |
| Polyoxyethylene glycol group | 117.2±30.5 |
| CoCl2 | 116.0±30.3 |
| MgCl2 | 113.1±31.5 |
| Embodiment 1 | 418.2±32.0** |
| Embodiment 2 | 421.0±31.1** |
Compare * P<0.05**P<0.01 with model group.
Claims (10)
1. the new compound structure being shown below, its structure is as follows:
A representation metal ion wherein, preferred calcium ion, magnesium ion, cobalt ion, barium ion, platinum ion, nickel ion, cupric ion.
2. the polymkeric substance of claim 1, wherein the molecular weight polyethylene glycol in polymkeric substance is 100-200000, the integer between m=1-5000, the preferably integer between m=1-2000.
3. the preparation method of compound as claimed in claim 1, is characterized in that:
1) the structure A that contains nitrilotriacetic acid(NTA)-Methionin reacts and obtains Compound C with compd B in sodium hydrogen carbonate solution;
2) Compound C with containing obtaining compd E after the star-like compound D stirring reaction of polyethylene glycol structures; Wherein the molecular weight polyethylene glycol in polymkeric substance is 100-200000;
3) compd E reacts to obtain compound F 17-hydroxy-corticosterone with metal ion compound;
Compd A;
Compd B;
Compound C;
Compound D, the integer between m=1-5000, the preferably integer between m=1-2000;
Compd E;
End product F, A representation metal ion.
4. the method for claim 3, wherein said chemical step selects solvent to be selected from: one or more in acetic acid, formic acid, benzene, toluene, pyridine, tetrahydrofuran (THF), trifluoroacetic acid, chloroform, tetracol phenixin, methylene dichloride, methyl alcohol, ethanol, methylene dichloride, dimethyl sulfoxide (DMSO), DMF.
5. the compound of claim 1, most preferred configuration is
With
Integer between m=1-5000, the preferably integer between m=1-2000.
6. the compound of claim 1 can be prepared into and be suitable for muscle, vein or the preparation of topical.
7. the described preparation of claim 6, it can be ordinary preparation, controlled release preparation, targeting preparation etc.
8. topical described in claim 6, is the various preparations for the direct administration of skin.
9. the compound of claim 1, described compound and pharmacologically acceptable salt thereof the purposes in the medicine of preparation treatment eczema.
10. the purposes of claim 9, the treatment of described eczema contains the treatment to acute, subacute and chronic eczema.
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| CN201310218702.2A CN104211950A (en) | 2013-06-04 | 2013-06-04 | Nonlinear polymer and preparation and use thereof |
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| CN201310218702.2A CN104211950A (en) | 2013-06-04 | 2013-06-04 | Nonlinear polymer and preparation and use thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104211949A (en) * | 2013-06-04 | 2014-12-17 | 韩文毅 | Nonlinear polymer and preparation and use thereof |
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| CN1829711A (en) * | 2003-04-11 | 2006-09-06 | 格兰马克药品股份有限公司 | Novel heterocyclic compounds useful for the treatment of inflammatory and allergic disorders: process for their preparation and pharmaceutical compositions containing them |
| WO2006138350A2 (en) * | 2005-06-15 | 2006-12-28 | Anormed Inc. | Chemokine receptor binding compounds |
| WO2010008864A2 (en) * | 2008-06-24 | 2010-01-21 | Amira Pharmaceuticals, Inc. | Cycloalkane[b]indole angtagonists of prostaglandin d2 receptors |
| CN101928318A (en) * | 2009-06-24 | 2010-12-29 | 天津金耀集团有限公司 | Preparation of fluorine-containing steroid hormone |
| CN104211949A (en) * | 2013-06-04 | 2014-12-17 | 韩文毅 | Nonlinear polymer and preparation and use thereof |
-
2013
- 2013-06-04 CN CN201310218702.2A patent/CN104211950A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1829711A (en) * | 2003-04-11 | 2006-09-06 | 格兰马克药品股份有限公司 | Novel heterocyclic compounds useful for the treatment of inflammatory and allergic disorders: process for their preparation and pharmaceutical compositions containing them |
| WO2006138350A2 (en) * | 2005-06-15 | 2006-12-28 | Anormed Inc. | Chemokine receptor binding compounds |
| WO2010008864A2 (en) * | 2008-06-24 | 2010-01-21 | Amira Pharmaceuticals, Inc. | Cycloalkane[b]indole angtagonists of prostaglandin d2 receptors |
| CN101928318A (en) * | 2009-06-24 | 2010-12-29 | 天津金耀集团有限公司 | Preparation of fluorine-containing steroid hormone |
| CN104211949A (en) * | 2013-06-04 | 2014-12-17 | 韩文毅 | Nonlinear polymer and preparation and use thereof |
Non-Patent Citations (2)
| Title |
|---|
| S. RAHIMA BENHABBOUR，ET AL.: ""In vitro and in vivo assessment of targeting lipid-based nanoparticles to the epidermal growth factor-receptor (EGFR) using a novel Heptameric ZEGFR domain"", 《JOURNAL OF CONTROLLED RELEASE》 * |
| SHARON WAICHMAN，ET AL.: ""Maleimide Photolithography for Single-Molecule Protein-Protein Interaction Analysis in Micropatterns"", 《ANALYTICAL CHEMISTRY》 * |
Cited By (1)
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| CN104211949A (en) * | 2013-06-04 | 2014-12-17 | 韩文毅 | Nonlinear polymer and preparation and use thereof |
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Application publication date: 20141217 |