CN101292952A - Glycyrrhizic acid, biogastrone acid or its salt, derivative temperature sensing gel rubber, preparation method and application thereof - Google Patents
Glycyrrhizic acid, biogastrone acid or its salt, derivative temperature sensing gel rubber, preparation method and application thereof Download PDFInfo
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Abstract
The invention relates to glycyrrhizic acid, glycyrrhetinic acid or glycyrrhetate, or derivative thermosensitive gel thereof, including 10-40 percent of poloxamer, 0.1-10 percent of carboxymethyl chitosan, 0.0001-10 percent of the glycyrrhizic acid, the glycyrrhetinic acid, the glycyrrhetate, the glycyrrhetinic acid salt or the derivative of the glycyrrhetinic acid, and 40-90.9 percent of water. The preparation method is as follows: the poloxamer is stirred evenly by adding water, the carboxymethyl chitosan is added to be stirred evenly as well, after the defoaming, the gel is added into the mixture until scattered and dissolved by stirring, and then the thermosensitive gel can be obtained by high-pressure sterilizing, filling and sealing; the medicine is the glycyrrhizic acid, the glycyrrhetinic acid, the glycyrrhetate and the glycyrrhetinic acid salt or the derivative of the glycyrrhetinic acid thereof. The invention can be used as a mucosa dosage preparation and an injection dosage preparation and can treat inflammatory bowel disease, stomatitis, oral ulcer, ocular inflammation and intracoelomic inflammations. The invention is convenient for clinical application, which can reduce the frequency of drug administration, improve the patient compliance, enhance the effectiveness of treatment and reduce toxicity and side effects.
Description
Technical field
The present invention relates to thermosensitive hydrogel and its production and application, relate more specifically to glycyrrhizic acid or enoxolone or its salt or derivatives thereof thermosensitive hydrogel and preparation and its medical usage.
Background technology
Root of Radix Glycyrrhizae and rhizome contain triterpenoid saponin glycyrrhizic acid (Glycyr-rhi zicacid), be glycyrrhizin (Glycyrrhizin), be enoxolone (chemical constitution and molecular formula are as follows for Glycyrrhetinicacid, glucosulfone aldehydic acid glycosides Glycyrrheticacid):
Glycyrrhizic acid molecular formula C
42H
62O
16
Enoxolone molecular formula C
30H
46O
4
Glycyrrhizic acid, enoxolone have effects such as antiinflammatory, antiulcer.Our research is also found, glycyrrhizic acid, enoxolone inflammatory bowel (IBD), rheumatic arthritis, gingivitis, periodontitis, oral ulcer have obvious curative effects, but, influenced its clinical practice owing to glycyrrhizic acid, the application of enoxolone whole body have the side effect of aldosterone sample.The research novel formulation changes route of administration, and the effect that strengthens topical application is the effective ways that solve side effect, improve curative effect.At present, local mucous membrane administration drug-delivery preparation commonly used is water preparation and gel, but water preparation is too short because of the local holdup time, be difficult to reach ideal treatment, and drug waste is very big; And gel thickness too makes very inconvenience of administration.Thermosensitive hydrogel has well remedied the defective of these two kinds of preparations, because of it at room temperature is in a liquid state, makes convenient drug administration, also because of it can be changed into gel state under 37 ℃ of body temperature, but the prolong drug local action time.
Summary of the invention
The present invention provides a kind of glycyrrhizic acid, enoxolone or its salt or derivatives thereof thermosensitive hydrogel and method for making and application at the problems referred to above exactly, this thermosensitive hydrogel is as mucosa delivery preparation and injecting and administering preparations, can treat inflammation in inflammatory bowel, oral inflammation, oral ulcer, eye inflammation, the body cavity, to make things convenient for clinical practice, reduce administration frequency, improve patient compliance; Strengthen therapeutic effect, reduce toxic and side effects.
One of technical scheme provided by the invention is: glycyrrhizic acid, enoxolone or its salt or derivatives thereof thermosensitive hydrogel, comprise: the derivant of 10-40% poloxamer, 0.1-10% carboxymethyl chitosan, 0.0001-10% glycyrrhizic acid, enoxolone, glycyrrhetate, glycyrrhetate or enoxolone, water 40-90.9%, above percentage ratio is weight percentage.
Described glycyrrhetate is dipotaccium glycyrrhizate, glycyrrhizic acid dipotassium, tripotassium glycyrrhetate, glycyrrhizic acid list sodium, disodium glycyrrhizinate, trisodium glycyrrhetinate, monoammonium glycyrrhizinate, diammonium glycyrrhizinate, glycyrrhizic acid three ammoniums, zinc glycyrrhetate, glycyrrhizic acid magnesium or aluminium glycyrrhetate.
Described glycyrrhetate is enoxolone potassium, enoxolone dipotassium, enoxolone tripotassium, Monosodium glycyrrhetin, enoxolone disodium, enoxolone trisodium, enoxolone zinc, enoxolone magnesium or enoxolone aluminum.
Described thermosensitive hydrogel pH value is 5-12.
Two of technical scheme provided by the invention is: the preparation method of above-mentioned thermosensitive hydrogel, contain the medicine of 10-40% poloxamer, 0.1-10% carboxymethyl chitosan, 0.0001-10%, the weight percent of water 40-90.9% by thermosensitive hydrogel, poloxamer is added water to stir, add carboxymethyl chitosan, stir, get gel behind the froth breaking, medicine is added gel, the dispersed with stirring dissolving, pressure sterilizing, fill, sealing obtain thermosensitive hydrogel; Described medicine is the derivant of glycyrrhizic acid, enoxolone, glycyrrhetate, glycyrrhetate or enoxolone.
Application in the medicine of above-mentioned thermosensitive hydrogel inflammation in preparation treatment inflammatory bowel, oral inflammation, oral ulcer, eye inflammation or body cavity.Inflammation in the described body cavity is as arthritis, cervical vertebra inflammation or lumbar vertebra inflammation etc.
The present invention induces rat colonitis with TNBS; coloclysis gives glycyrrhizic acid 50mg/kg, enoxolone methyl ester 1mg/kg thermosensitive hydrogel; once a day; after the administration 7 days; compare with the model group of not administration, damage has significant protective effect to colon, and blood K+, blood Na+ do not have significant change; show that glycyrrhizic acid, enoxolone methyl ester thermosensitive hydrogel can be with by intestinal mucosa drug treatment inflammatory bowel, and under therapeutic dose, do not see tangible untoward reaction.
The present invention induces rat arthritis model with Freund's complete adjuvant (AA), give glycyrrhizic acid 50mg/kg, enoxolone methyl ester 1mg/kg thermosensitive hydrogel in the articular cavity, weekly, after 3 weeks, compare with the model group of not administration, can obviously suppress rat paw edema, prolong hot plate and ease pain incubation period, show that thermosensitive hydrogel of the present invention can be used for the treatment of inflammation in the body cavity.
Experiment shows that the present invention can treat inflammation in inflammatory bowel, oral inflammation, oral ulcer, eye inflammation, the body cavity as mucosa delivery preparation and injecting and administering preparations, to make things convenient for clinical practice, reduces administration frequency, improves patient compliance; Strengthen therapeutic effect, reduce toxic and side effects.
Because glycyrrhizic acid and enoxolone water solublity are not ideal, although also can be prepared into stable formulation, technology is complicated, therefore, with its preparation salify, can increase water solublity, thereby reach the purpose of simplifying technology.In preparation inflammatory enteropathy medicine, earlier glycyrrhizic acid and enoxolone are made water-soluble glycyrrhetate and glycyrrhetate respectively.
Glycyrrhetate of the present invention can be dipotaccium glycyrrhizate, molecular formula: C
42H
61KO
16Glycyrrhizic acid dipotassium, molecular formula: C
42H
60K
2O
16Tripotassium glycyrrhetate, molecular formula: C
42H
59K
3O
16Glycyrrhizic acid list sodium, molecular formula: C
42H
61NaO
16Disodium glycyrrhizinate, molecular formula: C
42H
60Na
2O
16The molecular formula of trisodium glycyrrhetinate: C
42H
59Na
3O
16Monoammonium glycyrrhizinate, molecular formula: C
42H
65NO
16Diammonium glycyrrhizinate, molecular formula: C
42H
68N
2O
16Glycyrrhizic acid three ammoniums, molecular formula: C
42H
71N
3O
16The molecular formula of zinc glycyrrhetate: C
42H
60ZnO
16Glycyrrhizic acid magnesium, molecular formula: C
42H
60MgO
16Or aluminium glycyrrhetate, molecular formula: C
42H
59AlO
16
Glycyrrhetate of the present invention can be enoxolone potassium, molecular formula: C
30H
45KO
4The enoxolone dipotassium, molecular formula: C
30H
44K
2O
4The molecular formula of enoxolone tripotassium: C
30H
43K
3O
4Monosodium glycyrrhetin, molecular formula: C
30H
45NaO
4The enoxolone disodium, molecular formula: C
30H
42Na
2O
4The molecular formula of enoxolone trisodium: C
30H
43Na
3O
4The molecular formula of enoxolone zinc: C
30H
44ZnO
4Enoxolone magnesium, molecular formula: C
30H
44MgO
4Or enoxolone aluminum, molecular formula: C
30H
43AlO
4
Glycyrrhetic acid derivant of the present invention can be enoxolone methyl ester, molecular formula C
31H
48O
4Acetyl enoxolone methyl ester, molecular formula are C
33H
50O
511-deoxidation enoxolone, molecular formula are C
30H
48O
311-deoxidation enoxolone-3-O succinic acid half-ester, molecular formula are C
34H
52O
6Acetyl enoxolone aluminum, molecular formula are C
32H
51AlO
6
Description of drawings
Fig. 1 is the protective effect that glycyrrhizic acid, Enoxolone derivative-enoxolone methyl ester thermosensitive hydrogel damage the colitis rat colon.A: normal group aqueous solution group; B: model aqueous solution group; C: model+0.5% glycyrrhizic acid (50mg/kg) aqueous solution group; D: model+0.01% enoxolone methyl ester (1mg/kg) aqueous solution group; E: model+5% balsalazide sodium (500mg/kg) aqueous solution group; F: normal group thermosensitive hydrogel; G: model thermosensitive hydrogel group; H: model+0.5% glycyrrhizic acid (50mg/kg) thermosensitive hydrogel group; I: model+0.01% enoxolone methyl ester (1mg/kg) thermosensitive hydrogel group; J: model+5% balsalazide sodium (500mg/kg) thermosensitive hydrogel group;
Fig. 2 is the protective effect to the rats with arthritis joint injury of glycyrrhizic acid, Enoxolone derivative-enoxolone methyl ester thermosensitive hydrogel.A: normal group; B: model group; C: model+5% glycyrrhizic acid (5mg/kg) thermosensitive hydrogel group; D: model+0.05% enoxolone methyl ester (0.05mg/kg) thermosensitive hydrogel group; E: model+0.1% dexamethasone (0.1mg/kg) thermosensitive hydrogel group.
The specific embodiment
Embodiment 1: by 0.5% poloxamer, 10% carboxymethyl chitosan, 0.001% glycyrrhizic acid and the weight percent of excess water, poloxamer is added water to stir, add carboxymethyl chitosan, stir, behind the froth breaking, glycyrrhizic acid is added gel, the dispersed with stirring dissolving, pressure sterilizing, fill, sealing obtain thermosensitive hydrogel.The gelation temperature of this gel is 35.5 ℃, gelling time 5min.(pH7.4 value)
Embodiment 2: by 30% poloxamer, 0.2% carboxymethyl chitosan, 8% sodium glycyrrhetate and the weight percent of excess water, poloxamer is added water to stir, add carboxymethyl chitosan, stir, behind the froth breaking, sodium glycyrrhetate is added gel, the dispersed with stirring dissolving, pressure sterilizing, fill, sealing obtain thermosensitive hydrogel.The gelation temperature of this gel is 35 ℃, gelling time 5min.(pH value 8.0)
Embodiment 3: poloxamer 188,2% carboxymethyl chitosan, 1% glycyrrhizic acid three ammoniums and the weight percent of excess water of pressing poloxamer 407, the 17wt% of 20wt%, poloxamer is added water to stir, add carboxymethyl chitosan, stir, behind the froth breaking, glycyrrhizic acid three ammoniums are added gel, the dispersed with stirring dissolving, pressure sterilizing, fill, sealing obtain thermosensitive hydrogel.The gelation temperature of this gel is 32 ℃, gelling time 1min.(pH8.0 value)
Embodiment 4: replace the glycyrrhizic acid among the embodiment 1 can obtain similar result enoxolone.
According to embodiment 2 or 3, with dipotaccium glycyrrhizate, glycyrrhizic acid dipotassium, tripotassium glycyrrhetate, disodium glycyrrhizinate, trisodium glycyrrhetinate, monoammonium glycyrrhizinate, diammonium glycyrrhizinate, zinc glycyrrhetate, glycyrrhizic acid magnesium, aluminium glycyrrhetate, enoxolone potassium, the enoxolone dipotassium, the enoxolone tripotassium, Monosodium glycyrrhetin, the enoxolone disodium, the enoxolone trisodium, enoxolone zinc, enoxolone magnesium, enoxolone aluminum, the enoxolone methyl ester, acetyl enoxolone methyl ester, 11-deoxidation enoxolone, 11-deoxidation enoxolone-3-O succinic acid half-ester, Monosodium glycyrrhetin among the acetyl deoxidation enoxolone aluminium substitution embodiment 2 or glycyrrhizic acid three ammoniums among the embodiment 3 can obtain the result of similar embodiment 2 or embodiment 3.
Embodiment 5: Chinese medicine has the little characteristics of good effect, particularly toxic and side effects, often can play a significant role aspect chronic, the difficult diseases of treatment.Present embodiment selects glycyrrhizic acid, Enoxolone derivative-enoxolone methyl ester to prepare thermosensitive hydrogel, medicine as the anti-inflammatory disease, by setting up inflammatory bowel, the arthritic animal model of property, observation gives the therapeutical effect that glycyrrhizic acid, enoxolone methyl ester thermosensitive hydrogel are compared with ordinary preparation, is intended to develop a kind of new inflammatory diseases preparation.
Experimental result shows, adopt the administration of thermosensitive hydrogel preparation, the next day that colitis treatment being adopted once, arthritis treatment adopts and all obtains satisfactory effect weekly, compare with ordinary preparation administration once a day, no significant difference, showing that the thermosensitive hydrogel preparation has the effect that reduces the administration frequency, improves patient compliance, is a kind of good preparation that is used for the treatment of chronic inflammation disease.In carrying out glycyrrhizic acid, of the experiment of enoxolone methyl ester, find colitis rat serum potassium, the influence of blood sodium, glycyrrhizic acid, enoxolone methyl ester aqueous solution group, because administration number of times is more, hypernatremia, hypokalemic trend appear, but glycyrrhizic acid, enoxolone methyl ester thermosensitive hydrogel do not have obvious influence to blood potassium, blood sodium in therapeutic process, show and use the thermosensitive hydrogel preparation, when obtaining similar therapeutic effect, safety is more reliable.
In the experiment of resisting rheumatoid arthritis, also reconfirm, use thermosensitive hydrogel and realize intracavitary administration weekly, still can obtain excellent curative.
Materials and methods
Medicine and reagent glycyrrhizic acid by Shenzhen money good fortune Pharmaceutical provide, the enoxolone methyl ester, self-control; Balsalazide sodium is provided by Shanxi Ante Biological Pharmaceutical Co., Ltd.; The MPO detection kit, building up bio-engineering research by Nanjing is provided.
The ripe male SD rat of animal health, body weight 180～220g, male and female half and half are provided production licence number by Wuhan University's Experimental Animal Center: SCXK (Hubei Province) 2003-2004.The Mus feedstuff is purchased the Experimental Animal Center in Wuhan University.
Instrument: TG328A type analysis balance, ultraviolet spectrophotometer, high speed homogenizer etc.
Experimental technique
Animal grouping and processing: rat random packet: normal control group, model group, balsalazide sodium positive drug matched group, glycyrrhizic acid group, enoxolone methyl ester group.Wherein, coloclysis gives glycyrrhizic acid 50mg/Kg, enoxolone methyl ester 1mg/Kg respectively, balsalazide sodium group coloclysis gives balsalazide sodium 500mg/Kg for glycyrrhizic acid group, enoxolone methyl ester group.With above-mentioned five components is aqueous solution group and thermosensitive hydrogel group, and the water group is administered once every day, and the thermosensitive hydrogel group was administered once in per two days.Rat is with the modeling of 50%TNBS alcoholic solution coloclysis, and second day begins administration, and after 14 days, sacrifice of animal is dissected on ice, gets complete section colon, weighs, and calculates the colon organ index in modeling, carries out colitis (CMDI) scoring.Get colon and make 5% homogenate, for detecting MPO with the PBS buffer.
Detect index
Colon damage index (CMDI): get complete section colon, cut off enteric cavity along mesentery, perusal abdominal adhesions and colonic ulcer, congested situation are marked by table 1 colon standards of grading (CMDI).
Myeloperoxidase (MPO) (MPO) accurately takes by weighing tissue weight, and volume ratio is 1: 19 adding PBS buffering homogenate by weight, and multigelation behind the high-speed homogenization is made 5% intestinal homogenate, and the Lowry method detects protein content.Press the strict operation of MPO detection kit.
Table 1. colon damage index (CMDI) standards of grading
| General form | Scoring |
| Abdominal adhesions: | |
| No adhesion | 0 |
| Slight adhesion | 1 |
| Severe adhesion | 2 |
| Colonic ulcer and inflammation: | |
| Non Apparent Abnormality | 0 |
| Colon hyperemia, no ulcer | 1 |
| Hyperemia, no ulcer, intestinal wall obviously thickens | 2 |
| Ulcer 1 place thickens (surface is downright bad) without hyperemia or intestinal wall | 3 |
| Intestinal wall has the petechia | 4 |
| Ulcer 1 place, the companion is congested, inflammation | 5 |
| Ulcer 2 places, the companion is congested, inflammation | 6 |
| More than ulcer 2 places | 7 |
| The place of boring a hole | 8 |
| Perforation is more than 1 place | 9 |
| Animal dead | 10 |
Two marks add up to PTS.
Blood potassium, blood sodium determination: get determination of serum blood potassium, blood na concn.
Experimental result
Glycyrrhizic acid, enoxolone methyl ester are to inflammatory bowel mice colon organ coefficient, Damage coefficient, the active influence of MPO
As seen obvious the reducing inflammation property enteropathy mice colon edema of glycyrrhizic acid, enoxolone methyl ester is compared effect significantly with positive control drug, and the thermosensitive hydrogel group is compared with the aqueous solution group, and the administration frequency reduces, and curative effect is similar, the results are shown in accompanying drawing 1 and
Table 2.
Table .2 glycyrrhizic acid, enoxolone methyl ester are to inflammatory bowel rat colon organ coefficient, inflammation scoring, the active influence of MPO
(x±s，n＝8)
Compare * * P＜0.01 with normal group; Compare with model group
▲ ▲P＜0.01
3. glycyrrhizic acid, enoxolone methyl ester are to the influence of colitis rat serum potassium, blood sodium
As seen glycyrrhizic acid, enoxolone methyl ester aqueous solution group because administration number of times is more, hypernatremia, hypokalemic trend occur, but glycyrrhizic acid, enoxolone methyl ester thermosensitive hydrogel do not have obvious influence to blood potassium, blood sodium in therapeutic process, the results are shown in Table 3.Show and use the thermosensitive hydrogel preparation, when obtaining similar therapeutic effect, safety is more reliable.
Table .3 glycyrrhizic acid, enoxolone methyl ester to the influence of colitis rat serum potassium, blood sodium (x ± s, n=8)
Experiment conclusion
Glycyrrhizic acid, enoxolone methyl ester thermosensitive hydrogel can effectively be protected the damage of inflammatory bowel rat colon, and evident in efficacy, with respect to aqueous solution preparation, side effect is low.
Embodiment 6: present embodiment is selected glycyrrhizic acid, the enoxolone methyl ester thermosensitive hydrogel local injection medicine as resisting rheumatoid arthritis, by setting up arthritic animal model, inquire into glycyrrhizic acid, enoxolone methyl ester thermosensitive hydrogel to arthritic influence, be intended to select a kind of determined curative effect, arthritis medicine that toxicity is little.
Materials and methods
Medicine and reagent glycyrrhizic acid, enoxolone methyl ester are provided by Shenzhen money good fortune Pharmaceutical; The dexamethasone injection is provided by sky, Tianjin medicine pharmaceutcal corporation, Ltd.
The ripe rat of animal health, body weight 180～220g, male and female half and half are provided production licence number by Wuhan University's Experimental Animal Center: SCXK (Hubei Province) 2003-2004.Feedstuff is purchased the Experimental Animal Center in Wuhan University.
Experimental technique
Animal grouping and processing: rat random packet: normal control group, model group, glycyrrhizic acid group, enoxolone methyl ester group, dexamethasone positive drug matched group.With the Freund's complete adjuvant modeling, administration in the 12nd day after modeling, glycyrrhizic acid group, enoxolone methyl ester group, intraarticular injection gives glycyrrhizic acid 5mg/Kg, enoxolone methyl ester 0.05mg/Kg, dexamethasone 0.1mg/kg (administration volume 0.01mg/100g) respectively, weekly, and continuous three weeks.
Detect index:
Foot swelling: measure before the modeling about sufficient volume, and after measuring modeling, sufficient volume about administration 21 days subtracts sufficient volume before the modeling with modeling metapedes volume, removes sufficient volume before and after the normal group modeling
Foot swelling rate %=[(administration group modeling metapedes volume-administration group modeling metapedes volume)-(administration group modeling metapedes volume-administration group modeling metapedes volume)]/(administration group modeling metapedes volume-administration group modeling metapedes volume) * 100%
Hot plate pain pain threshold: regulate iron plate, constant temperature is put into rat at 50 ± 0.5 ℃, writes down it from putting into iron plate to the metapedes required time occurring licking, as the pain threshold of this Mus.
Experimental result
1. glycyrrhizic acid, enoxolone methyl ester are to the protective effect in rats with arthritis joint
By accompanying drawing 2 as seen, glycyrrhizic acid, enoxolone methyl ester thermosensitive hydrogel intracavitary administration can obviously improve the deformation extent in rats with arthritis joint.
2. glycyrrhizic acid, enoxolone methyl ester are to rats with arthritis foot swelling and the preclinical influence of hot plate pain
As seen glycyrrhizic acid, enoxolone methyl ester can obviously alleviate the foot swelling of ameliorate osteoarthritis rat, prolong hot plate pain incubation period, compare effect with positive control drug significantly, show that glycyrrhizic acid, enoxolone methyl ester thermosensitive hydrogel are obvious to arthritic antiinflammatory, analgesic activity, the results are shown in Table 4.
Table .4 glycyrrhizic acid, enoxolone methyl ester to rats with arthritis foot swelling and the preclinical influence of pain (x ± s, n=8)
Compare * * P＜0.01 with normal group; Compare with model group
▲ ▲P＜0.01
Claims (8)
1. a glycyrrhizic acid, enoxolone or its salt or derivatives thereof thermosensitive hydrogel, comprise: the derivant of 0.1-40% poloxamer, 0.1-10% carboxymethyl chitosan, 0.0001-10% glycyrrhizic acid, enoxolone, glycyrrhetate, glycyrrhetate or enoxolone, water 40-99.9999%, above percentage ratio is weight percentage.
2. according to the described thermosensitive hydrogel of claim 1, it is characterized in that: glycyrrhetate is dipotaccium glycyrrhizate, glycyrrhizic acid dipotassium, tripotassium glycyrrhetate, glycyrrhizic acid list sodium, disodium glycyrrhizinate, trisodium glycyrrhetinate, monoammonium glycyrrhizinate, diammonium glycyrrhizinate, glycyrrhizic acid three ammoniums, zinc glycyrrhetate, glycyrrhizic acid magnesium or aluminium glycyrrhetate
6
3. according to the described thermosensitive hydrogel of claim 1, it is characterized in that: glycyrrhetate is enoxolone potassium, enoxolone dipotassium, enoxolone tripotassium, Monosodium glycyrrhetin, enoxolone disodium, enoxolone trisodium, enoxolone zinc, enoxolone magnesium or enoxolone aluminum.
4. according to the described thermosensitive hydrogel of claim 1, it is characterized in that: Enoxolone derivative is enoxolone methyl ester, acetyl enoxolone methyl ester, 11-deoxidation enoxolone, 11-deoxidation enoxolone-3-0 succinic acid half-ester or acetyl enoxolone aluminum.
5. according to claim 1 or 2 or 3 or 4 described thermosensitive hydrogel, it is characterized in that: the thermosensitive hydrogel pH value is 5-12.
6. the method for making of claim 1 or 2 or 3 or 4 described thermosensitive hydrogel, it is characterized in that: contain the medicine of 10-40% poloxamer, 0.1-10% carboxymethyl chitosan, 0.0001-10%, the weight percent of water 40-90.9% by thermosensitive hydrogel, poloxamer is added water to stir, add carboxymethyl chitosan, stir, get gel behind the froth breaking, medicine is added gel, the dispersed with stirring dissolving, pressure sterilizing, fill, sealing obtain thermosensitive hydrogel; Described medicine is the derivant of glycyrrhizic acid, enoxolone, glycyrrhetate, glycyrrhetate or enoxolone.
7. the application in the medicine of claim 1 or 2 or 3 or 4 described thermosensitive hydrogel inflammation in preparation treatment inflammatory bowel, oral inflammation, oral ulcer, eye inflammation or body cavity.
8. application according to claim 7 is characterized in that: inflammation is arthritis, cervical vertebra inflammation or lumbar vertebra inflammation in the described body cavity.
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2008
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