CN101103994B - Medicine for preventing and treating gout and hyperuricemia - Google Patents
Medicine for preventing and treating gout and hyperuricemia Download PDFInfo
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- CN101103994B CN101103994B CN2006100910892A CN200610091089A CN101103994B CN 101103994 B CN101103994 B CN 101103994B CN 2006100910892 A CN2006100910892 A CN 2006100910892A CN 200610091089 A CN200610091089 A CN 200610091089A CN 101103994 B CN101103994 B CN 101103994B
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Abstract
The invention discloses medicine for treating and preventing hyperuricaemia and gout and the preparation method and application. The medicine of the invention contains a matter chosen from any of chitin, chitin quaternary ammonium salt and chitosan quaternary ammonium salt. The medicine of the invention can be produced as pulvis, troche or capsule. The medicine is made of chitin, the natural product extracted from shell of shrimp or crab, or made of chemical-modified ramification of chitin quaternary ammonium salt or chitosan quaternary ammonium salt, without any side effect; tests in animals prove that the medicine has both functions of excluding uric acid and restraining the forming of uric acid, therefore the invention has broader market development prospect and great social and economic benefit.
Description
Technical field
The present invention relates to the medicine of a kind of prevention and treatment gout and hyperuricemia.
Background technology
Gout and hyperuricemia are the metabolic diseases that purine metabolic disturbance causes.When the hematuria acid number, male＞416 are little rubs/liter, before women's menopause＞357 little rubbing/liter, can be judged to be hyperuricemia.When the hyperuricemia that continues causes arthralgia, promptly be referred to as gout.The prevalence of gout is approximately hyperuricemia patient's 5%～12% far below hyperuricemia.
In recent years, epidemiological studies shows that the prevalence of hyperuricemia and gout raises just year by year both at home and abroad, and serum uric acid level raises and obesity, disorders of lipid metabolism, diabetes and cardiovascular disease etc. are closely related, and hyperuricemia, gout have become the important diseases that threatens human health.
Hyperuricemia and gout still do not have the radical cure method now.After finding that blood uric acid is higher, generally need take the medicine of some easing pain and diminishing inflammations and uric acid resisting, with alleviating pain, make blood uric acid remain on normal range, prevent that uric acid from depositing in tissue, the outbreak of prophylaxis of acute gout, protection renal function.At present, the medicine for the treatment of gout and hyperuricemia clinically mainly contains three classes: 1. promote the medicine of urate excretion, and as benzbromarone, probenecid, sulphinpyrazone etc.; 2. the medicine that suppresses uricopoiesis, as allopurinol, only this is a kind of clinically now; 3. easing pain and diminishing inflammation class medicine is as colchicine, indometacin, phenylbutazone class, ibuprofen class, piroxicam, prednisone, dexamethasone etc.
Above-mentioned three class medicaments can only be used for mitigate the disease, take for a long time to produce many toxic and side effects.Can produce phenomenons such as nausea,vomiting,diarrhea, alopecia, myalgia, leukopenia, aplastic anemia as colchicine, severe patient can be suffered from hemorrhagic enteritis; Probenecid can cause nausea, inappetence, stomach discomfort, skin are itched, erythra, urticaria, leukopenia, thrombocytopenia and hemolytic anemia etc.; Though benzbromarone is more than probenecid safety, abnormal liver function, leucocytes reduction etc. can take place in only a few patient.
For the research of chitin and derivant thereof, existing both at home and abroad many reports.Great majority concentrate on the synthetic of research chitosan quaternary ammonium salt and characterize, the application of chitosan quaternary ammonium salt aspect daily-use chemical industry, sewage disposal, weaving, and the preparation of special macromolecular material, performance of keeping humidity, blood coagulation resisting function, accent blood fat, raise immunity and antitumor action etc.(Wuhan University's journal, 2003 02 phases) such as Xu Chen (applied chemistry,, 5 phases in 1996), Fan Mu studied the hygroscopicity and the performance of keeping humidity of chitosan quaternary ammonium derivant; Ou Yangwenzhu etc. (Xiangtan Normal College's journal, 2004 04 phases) adopt different phase method to prepare water miscible hydroxypropyltrimethyl ammonium chloride chitosan (HACC), have studied the application performance of this material in fabric sofetening is handled; Tian Defeng etc. (Chinese biochemical drug magazine,, 23 volumes, 6 phases in 2002) have carried out chitosan quaternary ammonium salt and have transferred blood fat research, and the result shows that chitosan quaternary ammonium salt can obviously reduce TC, TG, LDL-C level (P＜0.01); Awie F.Kotz é et al research has been compared chitosan and chitosan quaternary ammonium salt at intestinal cell permeability of the membrane energy; (Chinese biochemical drug magazine,, 26 volumes in 2005 such as Zhang Jianguo, the 2nd phase) studied the influence of low molecular n-trimethyl chitosan chloride to mice S180 and body's immunity, the result shows, low molecular n-trimethyl chitosan chloride can enhancing body's immunological function, and has tumor-inhibiting action.Viviane A.Spinelli, and Mauro C.M.Laranjeira and Valfredo T.F á vere (Functional Polymers, 2004,61 (3), 347-352) studied the adsorption equilibrium of chitosan quaternary ammonium salt pair chromium; Zhou Jun, Guo Shunzhi, Wu Xiangjiang (organosilicon material, 2004 18 3 phases of volume) are raw material with trimethylamine, epoxychloropropane, chitosan, have synthesized the N-chitosan quaternary ammonium salt, have made a kind of novel organosilicon softening agent.But up to the present, still useless chitin and derivant thereof are carried out the report of adsorption experiment aspect to uric acid, more do not have the example of finding such material is used to prevent and treat gout and hyperuricemia.
Summary of the invention
The purpose of this invention is to provide a kind of novel prevention and the medicine of treatment gout and hyperuricemia.
The medicine of prevention of the present invention and treatment gout and hyperuricemia comprises: a kind ofly be selected from the chemical compound that construction unit satisfies structural formula (I),
Wherein, R
0Be selected from hydrogen atom, the structural formula chlorination quaternary ammonium ion shown in (II);
R ' is selected from hydrogen atom, acetyl group and the structural formula chlorination quaternary ammonium ion shown in (II);
R, R
1, R
3Being selected from carbon number is C
1-C
3Alkyl, R, R
1, R
3Can be identical or inequality, R
2Be selected from the propyl group that hydroxyl replaces;
In a preferred embodiment of the invention, medicine of the present invention comprise construction unit shown in structural formula (I), R ' is for the chitin of acetyl group and/or be selected from a kind of chemical compound in the quaternary ammonium salt derivative of above-mentioned chitin; Wherein, R, R
1, R
3Being selected from carbon number is C
1-C
3Alkyl, as methyl, ethyl, propyl group, R
2Be the propyl group that hydroxyl replaces, preferred 2-hydroxyl n-pro-pyl; And the substitution value of described chitin quaternary ammonium salt derivative is 10-100%.More preferably, medicine of the present invention comprises chitin or O-hydroxypropyl-trimethyl ammonium chloride chitin, and the substitution value of wherein said O-hydroxypropyl-trimethyl ammonium chloride chitin is 10-100%.
In another preferred embodiment of the present invention, medicine of the present invention comprises a kind of chitosan quaternary ammonium salt derivatives, and described chitosan quaternary ammonium salt derivatives comprises
Construction unit shown in structural formula (I), R
0For hydrogen atom, R ' is the N-chitosan quaternary ammonium salt of the chlorination quaternary ammonium ion shown in structural formula (II);
Construction unit shown in the structural formula (I), R
0Be the chlorination quaternary ammonium ion of structural formula shown in (II), R ' is the O-chitosan quaternary ammonium salt of hydrogen atom;
With construction unit shown in the structural formula (I), R
0, R ' is the N of the chlorination quaternary ammonium ion of structural formula shown in (II), the O-chitosan quaternary ammonium salt; Wherein said O-chitosan quaternary ammonium salt, N-chitosan quaternary ammonium salt and N, the quaternary ammonium ion in the O-chitosan quaternary ammonium salt are selected from the quaternary ammonium ion of identical structural formula shown in (II); And R, R
1, R
3Being selected from carbon number is C
1-C
3Alkyl, as methyl, ethyl, propyl group, R
2Be the propyl group that hydroxyl replaces, preferred 2-hydroxyl n-pro-pyl.
That is to say that the O-that comprises in the same a kind of chitosan quaternary ammonium salt in the described medicine replaces, N replaces, N, the disubstituted chitosan quaternary ammonium salt of O is that chitosan is obtained by identical quaternary ammonium ion replacement.
More preferably, chitosan quaternary ammonium salt derivatives described in the medicine of the present invention is a hydroxypropyltrimethyl ammonium chloride chitosan, it comprises the O-hydroxypropyltrimethyl ammonium chloride chitosan, N-hydroxypropyltrimethyl ammonium chloride chitosan and N, O-hydroxypropyltrimethyl ammonium chloride chitosan;
Wherein, the substitution value of described O-hydroxypropyltrimethyl ammonium chloride chitosan, N-hydroxypropyltrimethyl ammonium chloride chitosan is 10-100%; Described N, the substitution value of O-hydroxypropyltrimethyl ammonium chloride chitosan are 10-200%.
In a preferred embodiment of the invention, medicine of the present invention comprises a kind of material that is selected from chitin, hydroxypropyl-trimethyl ammonium chloride chitin and the hydroxypropyltrimethyl ammonium chloride chitosan.
The substitution value of chitosan quaternary ammonium salt that medicine of the present invention is included or chitin quaternary ammonium salt (DS) is measured by the following method: accurately take by weighing sample behind the purification, with using AgNO behind the dissolved in distilled water
3Cl in the standard solution titration sample
-, and calculate substitution value with following formula:
The AgNO that V-consumes
3Volume, mL;
M-AgNO
3Molar concentration, molL
-1
W-example weight g;
161-cell enclosure polysaccharide molecular weight;
314 is the molecular weight of unit chitosan quaternary ammonium salt.
In the concrete enforcement of medicine of the present invention, preferred dosage form is tablet or capsule.
In medicine of the present invention, also can contain and make required auxiliary agent of above-mentioned dosage form such as excipient etc. in the prior art.
In a preferred embodiment of the invention, medicine of the present invention is by chitin or chitosan and 2, and 3-glycidyl tri alkyl ammomium chloride prepared in reaction obtains.In concrete enforcement, can directly use commercially available chitin or chitosan product, also can use step (1), (2) in the following method to prepare chitin or chitosan.
Preferably, it prepares by the method that may further comprise the steps:
(1) Crusta Penaeus seu Panulirus or Carapax Eriocheir sinensis are cleaned, sour decalcification, the alkali isolating protein, washing, drying is pulverized and is made chitin;
(2) chitin that step (1) the is obtained deacetylated chitosan that gets of 40-50%NaOH;
(3) chitosan that obtains of chitin that step (1) is obtained or step (2), organic alcohols solvent add in the there-necked flask, heating in water bath, be warming up to 80～90 ℃ under stirring, add the quaternary ammonium salt aqueous solution shown in structural formula (II) again, constant temperature stirring reaction 8～24h, product after filtration, washing, sucking filtration, drying, obtain the chemical compound that medicine of the present invention comprises;
(4) chemical compound that obtains of chitin that step (1) is obtained or step (3) is made capsule, or adds a small amount of excipient and be pressed into tablet, makes medicine of the present invention.
The present invention also provides a kind of preparation method of medicine of the present invention.
Medicine of the present invention can adopt the method for preparing chitin, chitin quaternary ammonium salt, chitosan quaternary ammonium salt of the prior art to prepare.Preferred employing method provided by the invention, with the natural prodcuts chitin that extracts from shrimp, Carapax Eriocheir sinensis is raw material, or be prepared into O-hydroxypropyl-trimethyl ammonium chloride chitin or N-hydroxypropyltrimethyl ammonium chloride chitosan or N, O-hydroxypropyltrimethyl ammonium chloride chitosan through chemical modification.
Concrete, the preparation method of the medicine of prevention of the present invention and treatment gout and hyperuricemia, it may further comprise the steps:
(1) Crusta Penaeus seu Panulirus or Carapax Eriocheir sinensis are cleaned, sour decalcification, the alkali isolating protein, washing, drying is pulverized and is made chitin;
(2) chitin that step (1) the is obtained deacetylated chitosan that gets of 40-50%NaOH;
(3) chitosan that obtains of chitin that step (1) is obtained or step (2), organic alcohols solvent add in the there-necked flask, heating in water bath, be warming up to 80～90 ℃ under stirring, add 2 again, 3-epoxypropyl trimethylammonium chloride aqueous ammonium, constant temperature stirring reaction 8～24h, product after filtration, washing, sucking filtration, drying, obtain the chemical compound that medicine of the present invention comprises;
(4) chemical compound that obtains of chitin that step (1) is obtained or step (3) is made capsule, or adds a small amount of excipient and be pressed into tablet, makes medicine of the present invention.
In described step (1), with the decalcification of 4-8% hydrochloric acid, after washing, reuse 10%NaOH isolating protein;
In described step (3), use isopropyl alcohol to make solvent, quaternary ammonium salt aqueous solution uses 2,3-epoxypropyl trimethylammonium chloride aqueous ammonium, obtain O-hydroxypropyl-trimethyl ammonium chloride chitin, comprise N-hydroxypropyltrimethyl ammonium chloride chitosan, O-hydroxypropyltrimethyl ammonium chloride chitosan and N, the hydroxypropyltrimethyl ammonium chloride chitosan of O-bis-hydroxypropyl trimethyl ammonium chloride chitosan.
Wherein step (1) or (2) are not necessary, can use commercially available chitin or chitosan directly to carry out step (3), (4), prepare medicine of the present invention.
The present invention also provides the application of medicine in prevention and treatment gout or hyperuricemia of prevention of the present invention and treatment gout and hyperuricemia.Concrete, the invention provides chitin and chitin quaternary ammonium salt thereof, the new purposes of chitosan quaternary ammonium salt in prevention and treatment gout or hyperuricemia.
Under simulation human body temperature, human intestines and stomach's wriggling situation, medicine of the present invention has been carried out in-vitro simulated absorption uric acid test; Also medicine of the present invention has been carried out animal experiment; The result proves that medicine of the present invention has the uric acid of inhibition and uricotelic dual function.
Do not find that medicine of the present invention has tangible toxicity.
The advantage of the medicine of prevention of the present invention and treatment gout and hyperuricemia is: medicine of the present invention is to be primary raw material with the natural prodcuts chitin that extracts from shrimp, Carapax Eriocheir sinensis, prepare through chemical modification, without any side effects to human body, have safety.
Description of drawings
Fig. 1, Fig. 2 are the infrared spectrograms of medicine of the present invention.
Wherein, a curve among Fig. 1 is the infrared spectrum of chitosan CTS, and the b curve is the infrared spectrum of the chitosan quaternary ammonium salt CTSJ that obtains of embodiments of the invention 3; C curve among Fig. 2 is the infrared spectrum of chitin CT, and the d curve is the infrared spectrum of the chitin quaternary ammonium salt CTJ that obtains of embodiments of the invention 2.
Medicine to be analyzed is carried out infrared spectrum analysis with the kBr mixed pressuring plate respectively, and analytical instrument is Tensor27.
Relatively two curves of a, b can find out that a curve is at 1031cm-1，1080cm
-1I and II alcoholic extract hydroxyl group C-O stretching vibration absworption peak, in the infrared spectrum of b curve, decrease, this may be because C6On primary alconol-OH the reason (Lin Youwen, synthetic chemistry, the 2nd phase of 2000, the 8 volumes) that some substitution reaction has generated the O-chitosan quaternary ammonium salt has occured; 1483cm in the b curve-1And 3018cm-1The place new absworption peak has appearred, be respectively quaternary ammonium group-CH3Deformation vibration peak and stretching vibration peak, show that nucleophilic substitution has occured hydroxyl, the amino in the chitosan molecule, generated the chitosan quaternary ammonium salt that N, O replace.
Compare two curves of c, d, typical difference is: 1031cm in (1) c infrared spectrogram-1，1080cm
-1I and II alcoholic extract hydroxyl group C-O stretching vibration absworption peak, in d, decrease, this may be C6On primary alconol-OH substitution reaction has occured has generated O-chitin quaternary ammonium salt (high gorgeous, Journal of Functional Polymers, the 1st phase of 2004, the 17 volumes); (2) amino N-H deformation vibration peak (1560cm no longer appears in curve c-1), and at 1482cm-1The new absworption peak of deformation vibration of quaternary ammonium group-CH has appearred in the place, shows that nucleophilic substitution has occured the hydroxyl in the chitin molecule, has generated chitin quaternary ammonium salt.
The specific embodiment
Crusta Penaeus seu Panulirus or Carapax Eriocheir sinensis are cleaned, and at room temperature the 4-8% hydrochloric acid solution with 10 times of amounts soaks the 24h decalcification.The disacidify liquid that inclines is washed to neutrality, boils 6h～8h with 10 times of amount 10%NaOH, removes protein wherein.The lixiviating liquid that inclines is washed to neutrality, soaks 1h with 5g/L KMnO4, filter, and washing, reuse 10g/L oxalic acid aqueous solution stirs decolouring down at 60 ℃～70 ℃, is washed to neutrality, and drying is pulverized and is made chitin, adds an amount of excipient and is pressed into tablet.
Embodiment 2
Chitin is (commercially available, white, lamellar, nitrogen content 6.2-6.9%, ash is less than 1.0%) be crushed to the 80-100 order after, take by weighing 10g and place three-neck flask, add the 90ml isopropyl alcohol, be warming up to 60 ℃ under stirring, 2 of adding 50%, 3-epoxypropyl trimethylammonium chloride aqueous ammonium 90ml, be warming up to 80-85 ℃, constant temperature stirring reaction 18h, age overnight, pour out supernatant, isopropyl alcohol 100ml washing precipitation with 85% 3 times, a small amount of washed with isopropyl alcohol of reuse 2 times, 80 ℃ of dryings, get medicine O-hydroxypropyl-trimethyl ammonium chloride chitin of the present invention, make capsule.
The chitin that embodiment 1 is prepared boils 4h with the 40-50%NaOH solution of 10 times of amounts, and the lixiviating liquid that inclines is washed to neutrality, and drying is pulverized and made chitosan; Its physical parameter is as follows:
Outward appearance: white powder; Ash (%):＜1.5; Moisture: 10%; Deacetylation (%): 80～95;
Viscosity (mpas): in (100～800)
Then, claim the 5g chitosan to place three-neck flask, add the 45ml isopropyl alcohol, heating in water bath is warming up to 60 ℃ under stirring, add again 50% 2,3-epoxypropyl trimethylammonium chloride aqueous ammonium 36ml is warming up to 80-85 ℃, constant temperature stirring reaction 12h, age overnight is poured out supernatant, the isopropyl alcohol 50ml washing precipitation with 85% 3 times, the a small amount of washed with isopropyl alcohol of reuse 2 times, 80 ℃ of dryings obtain hydroxypropyltrimethyl ammonium chloride chitosan, add a small amount of excipient and be pressed into tablet, obtain medicine of the present invention.
Under simulation human body temperature, human intestines and stomach's wriggling situation, the medicine that contains chitin, chitin quaternary ammonium salt and chitosan quaternary ammonium salt that embodiment 1-3 is obtained has carried out in-vitro simulated absorption uric acid experiment, and test method and result are as follows:
(1) method
Get the certain density uric acid test solution that 30ml prepares and put into tool plug triangular flask, add a certain amount of chitin or derivatives thereof, place in the TZ-2DH constant-temperature shaking culture case, temperature is controlled at 36.5-37.0 ℃, with 120 rev/mins of joltings 6 hours, takes out triangular flask, test solution filters in color-comparison tube, measure uric acid content in the solution with daily output 7060 automatic clinical chemistry analyzers, each sample repeats 2 times, calculates the adsorption rate of various dose medicine to uric acid with following formula:
(2) result
The results are shown in Table 1.As can be seen from Table 1, chitin, chitin quaternary ammonium salt and chitosan quaternary ammonium salt pair uric acid have very strong absorbability, and especially chitosan quaternary ammonium salt adds dosage 0.06g, and 97% uric acid is adsorbed in the solution.
Table 1 medicine absorption of the present invention uric acid experimental result
Tested number medication name dose (g) adsorption rate (%)
0 blank 00
1 chitin 0.75 18.3
2 chitin quaternary ammonium salts 0.1 22.6
3 chitin quaternary ammonium salts 0.2 36.4
4 chitin quaternary ammonium salts 0.3 47.7
5 chitin quaternary ammonium salts 0.4 54.3
6 chitin quaternary ammonium salts 0.5 60.3
7 chitin quaternary ammonium salts 0.75 69.7
8 chitosan quaternary ammonium salts 0.02 50.8
9 chitosan quaternary ammonium salts 0.04 91.4
10 chitosan quaternary ammonium salts 0.06 97.9
11 chitosan quaternary ammonium salts 0.1 97.0
Embodiment 5
The medicine that uses the embodiment of the invention 3 to obtain has carried out the test of animal releasing uric acid and has suppressed the uricopoiesis test.Test method is as follows:
(1) experimental animal: 56 of one-level Kunming mouses, male, body weight 25-28 gram is provided by China Academy of TCM.Animal is divided into five groups at random, 10 of normal control groups, 16 of model control group, each 10 of high, medium and low dosage groups.
(2) test preparation: white or pale yellow powder, be dissolved in distilled water, it is stand-by to be divided into basic, normal, high three dosage.
Low dosage: be made into 5mg/ml solution with distilled water, feed 0.2ml/10g body weight (100mg/kg);
Middle dosage: be made into 10mg/ml solution with distilled water, feed 0.2ml/10g body weight (100mg/kg);
High dose: be made into 20mg/ml solution with distilled water, feed 0.2ml/10g body weight (100mg/kg);
Uric acid compound method: take by weighing the 800mg uric acid, grind with 0.75% carboxymethyl cellulose and be made into 40mg/ml, 20mg/ml suspension.
Hypoxanthine compound method (1000mg/kg): take by weighing the 1.25g hypoxanthine, with the 0.5%NaOH dissolving, transfer PH to 6.0 with 1NHCl then earlier.
(3) with uric acid moulding test method: model control group and normal control group, lumbar injection distilled water, test group intraperitoneal injection three days.Model control group and test group lumbar injection 0.75% carboxymethyl cellulose uric acid suspension (0.2ml/10gB.W) in the 4th administration, 2h after the moulding, the socket of the eye venous blood collection is measured uric acid content in the blood.
(4) use the hypoxanthine formative method: model control group and normal control group, lumbar injection distilled water, test group intraperitoneal injection three days.Model control group and test group Intraperitoneal injection of hypoxanthine supernatant liquid (0.2ml/10gB.W) in the 4th administration, 2h after the moulding, the socket of the eye venous blood collection is measured uric acid content in the blood.
(5) result of the test:
Use the hypoxanthine formative method, from table 2 result as seen, model is set up (p＜0.01), compares with model control group, and uric acid obviously reduces (p＜0.05) in the high dose group blood.
With uric acid moulding test method, from table 3 result as seen, model is set up (p＜0.01), compares with model control group, and uric acid obviously reduces (p＜0.05) in middle dosage group, the high dose group blood.
Table 2 medicine of the present invention is to the influence (hypoxanthine formative method) of experimental animal blood uric acid
| Project | The normal control group | Model control group | Middle dosage group | High dose group |
| Blood uric acid (mmol/L) | 0.141±0.059 | 0.502±0.237 | 0.517±0.102 | 0.352±0.113 * |
| p | 0.00002 | 0.8220 | 0.0414 |
*P (T check)＜0.05 is compared in expression with model control group
Table 3 medicine of the present invention is to the influence of experimental animal blood uric acid
| Project | The normal control group | Model control group | Low dose group | Middle dosage group | High dose group |
| Blood uric acid (mmol/L) | 0.238±0.056 | 0.313±0.067 | 0.289±0.048 | 0.2667±0.036 | 0.249±0.055 |
| p | 0.0053 | 0.334 | 0.0388 | 0.0256 |
Evidence, medicine of the present invention have the uric acid of inhibition and uricotelic dual function.
Claims (12)
1. the medicine of a prevention and treatment gout and hyperuricemia is characterized in that this medicine comprises to be selected from the chemical compound that construction unit satisfies structural formula (I),
Wherein, R
0Be selected from hydrogen atom, the structural formula chlorination quaternary ammonium ion shown in (II);
R ' is selected from hydrogen atom, acetyl group and the structural formula chlorination quaternary ammonium ion shown in (II); R
0, R ' is not hydrogen atom simultaneously; When R ' is acetyl group, R
0Be the chlorination quaternary ammonium ion of structural formula shown in (II);
R, R
1, R
3Being selected from carbon number is C
1-C
3Alkyl, R, R
1, R
3Can be identical or inequality, R
2Be the propyl group of hydroxyl replacement,
Described medicine is tablet or capsule.
2. according to the described medicine of claim 1, it is characterized in that this medicine comprise be selected from construction unit shown in structural formula (I), R ' is a kind of chemical compound in the chitin quaternary ammonium salt derivative of acetyl group; Wherein, R, R
1, R
3Be methyl, ethyl or propyl group, R
2Propyl group for the hydroxyl replacement;
The substitution value of described chitin quaternary ammonium salt derivative is 10-100%.
3. according to the described medicine of claim 2, it is characterized in that this medicine comprises O-hydroxypropyl-trimethyl ammonium chloride chitin, the substitution value of wherein said O-hydroxypropyl-trimethyl ammonium chloride chitin is 10-100%.
4. according to the described medicine of claim 1, it is characterized in that this medicine comprises a kind of chitosan quaternary ammonium salt derivatives, described chitosan quaternary ammonium salt derivatives comprises
Construction unit shown in the structural formula (I), R
0For hydrogen atom, R ' is the N-chitosan quaternary ammonium salt of the chlorination quaternary ammonium ion of structural formula shown in (II);
Construction unit shown in the structural formula (I), R
0Be the chlorination quaternary ammonium ion of structural formula shown in (II), R ' is the O-chitosan quaternary ammonium salt of hydrogen atom;
With construction unit shown in the structural formula (I), R
0, R ' is the N of the chlorination quaternary ammonium ion of structural formula shown in (II), the O-chitosan quaternary ammonium salt;
Wherein said O-chitosan quaternary ammonium salt, N-chitosan quaternary ammonium salt and N, the quaternary ammonium ion in the O-chitosan quaternary ammonium salt are selected from the quaternary ammonium ion of identical structural formula shown in (II); And R, R
1, R
3Be methyl, ethyl or propyl group, R
2Propyl group for the hydroxyl replacement.
5. medicine according to claim 4, it is characterized in that described chitosan quaternary ammonium salt derivatives is a hydroxypropyltrimethyl ammonium chloride chitosan, it comprises the O-hydroxypropyltrimethyl ammonium chloride chitosan, N-hydroxypropyltrimethyl ammonium chloride chitosan and N, O-hydroxypropyltrimethyl ammonium chloride chitosan;
Wherein, the substitution value of described O-hydroxypropyltrimethyl ammonium chloride chitosan, N-hydroxypropyltrimethyl ammonium chloride chitosan is 10-100%;
Described N, the substitution value of O-hydroxypropyltrimethyl ammonium chloride chitosan are 10-200%.
6. according to the described medicine of one of claim 1-5, it is characterized in that described medicine is by chitin or chitosan and 2,3-glycidyl tri alkyl ammomium chloride prepared in reaction obtains.
7. according to the described medicine of claim 6, it is characterized in that it prepares by the method that may further comprise the steps:
(1) Crusta Penaeus seu Panulirus or Carapax Eriocheir sinensis are cleaned, sour decalcification, the alkali isolating protein, washing, drying is pulverized and is made chitin;
(2) chitin that step (1) the is obtained deacetylated chitosan that gets of 40-50%NaOH;
(3) chitosan that obtains of chitin that step (1) is obtained or step (2), organic alcohols solvent add in the there-necked flask, heating in water bath, be warming up to 80～90 ℃ under stirring, add 2 again, 3-glycidyl tri alkyl ammomium chloride aqueous solution, constant temperature stirring reaction 8～24h, product after filtration, washing, sucking filtration, drying, obtain the chemical compound that medicine of the present invention comprises;
(4) chemical compound that step (3) is obtained is made capsule, or adds a small amount of excipient and be pressed into tablet, makes medicine of the present invention.
8. the preparation method of the medicine of the described prevention of one of claim 1-7 and treatment gout and hyperuricemia, it may further comprise the steps:
(1) Crusta Penaeus seu Panulirus or Carapax Eriocheir sinensis are cleaned, sour decalcification, the alkali isolating protein, washing, drying is pulverized and is made chitin;
(2) chitin that step (1) the is obtained deacetylated chitosan that gets of 40-50%NaOH;
(3) chitosan that obtains of chitin that step (1) is obtained or step (2), organic alcohols solvent add in the there-necked flask, heating in water bath, be warming up to 80～90 ℃ under stirring, add 2 again, 3-glycidyl tri alkyl ammomium chloride aqueous solution, constant temperature stirring reaction 8～24h, product after filtration, washing, sucking filtration, drying, obtain the chemical compound that medicine of the present invention comprises;
(4) chemical compound that step (3) is obtained is made capsule, or adds a small amount of excipient and be pressed into tablet, makes medicine of the present invention.
9. preparation method according to claim 8 is characterized in that:
In described step (1), with the decalcification of 4-8% hydrochloric acid, after washing, reuse 10%NaOH isolating protein;
In described step (3), use isopropyl alcohol to make solvent, quaternary ammonium salt aqueous solution uses 2,3-epoxypropyl trimethylammonium chloride aqueous ammonium, obtain O-hydroxypropyl-trimethyl ammonium chloride chitin, comprise N-hydroxypropyltrimethyl ammonium chloride chitosan, O-hydroxypropyltrimethyl ammonium chloride chitosan and N, the hydroxypropyltrimethyl ammonium chloride chitosan of O-hydroxypropyltrimethyl ammonium chloride chitosan.
10. the application of chitosan quaternary ammonium salt in the medicine of preparation prevention and treatment gout and hyperuricemia, it is characterized in that: described chitosan quaternary ammonium salt is the chemical compound that construction unit satisfies structural formula (I),
Wherein, R
0Be selected from hydrogen atom, the structural formula chlorination quaternary ammonium ion shown in (II);
R ' is selected from hydrogen atom, the structural formula chlorination quaternary ammonium ion shown in (II); R
0, R ' is not hydrogen atom simultaneously;
R, R
1, R
3Being selected from carbon number is C
1-C
3Alkyl, R, R
1, R
3Can be identical or inequality, R
2Propyl group for the hydroxyl replacement.
11. application according to claim 10 is characterized in that: described chitosan quaternary ammonium salt comprises construction unit shown in the structural formula (I), R
0For hydrogen atom, R ' is the N-chitosan quaternary ammonium salt of the chlorination quaternary ammonium ion of structural formula shown in (II);
Construction unit shown in the structural formula (I), R
0Be the chlorination quaternary ammonium ion of structural formula shown in (II), R ' is the O-chitosan quaternary ammonium salt of hydrogen atom;
With construction unit shown in the structural formula (I), R
0, R ' is the N of the chlorination quaternary ammonium ion of structural formula shown in (II), the O-chitosan quaternary ammonium salt;
Wherein said O-chitosan quaternary ammonium salt, N-chitosan quaternary ammonium salt and N, the quaternary ammonium ion in the O-chitosan quaternary ammonium salt are selected from the quaternary ammonium ion of identical structural formula shown in (II); And R, R
1, R
3Be methyl, ethyl or propyl group, R
2Propyl group for the hydroxyl replacement.
12. application according to claim 11, it is characterized in that: described chitosan quaternary ammonium salt is a hydroxypropyltrimethyl ammonium chloride chitosan, it comprises the O-hydroxypropyltrimethyl ammonium chloride chitosan, N-hydroxypropyltrimethyl ammonium chloride chitosan and N, O-hydroxypropyltrimethyl ammonium chloride chitosan;
Wherein, the substitution value of described O-hydroxypropyltrimethyl ammonium chloride chitosan, N-hydroxypropyltrimethyl ammonium chloride chitosan is 10-100%;
Described N, the substitution value of O-hydroxypropyltrimethyl ammonium chloride chitosan are 10-200%.
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| CN105456289A (en) * | 2015-12-08 | 2016-04-06 | 杜玉茗 | Composite western medicine formula for treating gout |
| CN114259507B (en) * | 2021-12-27 | 2022-09-16 | 暨南大学 | Application of klebsiella minutissima in preparing medicine for treating and/or preventing hyperuricemia related diseases |
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Non-Patent Citations (5)
| Title |
|---|
| Yongmei Xu et al..Preparation and modification of N-(2-hydroxyl)propyl-3-trimethylammonium chitosan chloride nanoparticle as a protein carrier.Biomaterials 24.2003,(24),5015-5022. * |
| 张建国等.低分子壳聚糖季按盐对小鼠实体瘤及其免疫系统的影响.中国生化药物杂志26 2.2005,26(2),93-95. * |
| 李铭等.羟丙基三甲基氯化铵壳聚糖在化妆品中的应用研究.化工科技市场 3.2004,(3),15-17. * |
| 田德峰等.氯化壳聚糖季按盐的调血脂活性研究.中国生化药物杂志23 6.2002,23(6),274-277. * |
| 高艳丽等.不同晶型甲壳索的季铵盐化研究.功能高分子学报17 1.2004,17(1),67-70. * |
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