CN101103994A - Medicine for preventing and treating gout and hyperuricemia - Google Patents
Medicine for preventing and treating gout and hyperuricemia Download PDFInfo
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- CN101103994A CN101103994A CNA2006100910892A CN200610091089A CN101103994A CN 101103994 A CN101103994 A CN 101103994A CN A2006100910892 A CNA2006100910892 A CN A2006100910892A CN 200610091089 A CN200610091089 A CN 200610091089A CN 101103994 A CN101103994 A CN 101103994A
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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 invention relates to a medicine for preventing and treating gout and hyperuricemia.
Background
Gout and hyperuricemia are metabolic diseases caused by purine metabolic disorders. And when the blood uric acid value is more than 416 micromoles/liter for men and more than 357 micromoles/liter for women before menopause, the hyperuricemia can be judged. When persistent hyperuricemia causes joint pain, it is called gout. The prevalence of gout is much lower than hyperuricemia, about 5% to 12% of patients with hyperuricemia.
In recent years, a large number of epidemiological studies at home and abroad show that the prevalence rate of hyperuricemia and gout is increasing year by year, the increase of the blood uric acid level is closely related to obesity, lipid metabolism disorder, diabetes, cardiovascular diseases and the like, and the hyperuricemia and the gout become important diseases threatening the health of human beings.
No radical cure method for hyperuricemia and gout exists at present. When the blood uric acid is high, some medicines for easing pain, diminishing inflammation and reducing uric acid are generally required to be taken to relieve pain, keep the blood uric acid in a normal range, prevent the deposition of uric acid in tissues, prevent the attack of acute gout and protect the kidney function. At present, the medicines for clinically treating gout and hyperuricemia mainly comprise three types: (1) drugs for promoting uric acid excretion, such as benzbromarone, probenecid, and metsulazolone; (2) drugs that inhibit uric acid production, such as allopurinol, are currently only one clinically; (3) analgesic and anti-inflammatory drugs such as colchicine, indomethacin, baotang, ibuprofen, YANTONGXIKANG, prednisone, dexamethasone, etc.
The three medicines can only be used for relieving the illness state, and can generate a plurality of toxic and side effects after long-term administration. For example, the hydrangeamine can cause nausea, vomiting, diarrhea, alopecia, myalgia, leukopenia, aplastic anemia, etc., and severe patients can suffer from hemorrhagic enteritis; probenecid can cause nausea, anorexia, stomach discomfort, skin itching, rash, urticaria, leukopenia, thrombocytopenia, hemolytic anemia, etc.; although benzbromanone is far safer than probenecid, few patients can have abnormal liver function, leucopenia and the like.
Many reports have been made on the study of chitin and its derivatives at home and abroad. Most of the researches are focused on the synthesis and characterization of the chitosan quaternary ammonium salt, the application of the chitosan quaternary ammonium salt in daily chemical industry, sewage treatment and textile, the preparation of special high polymer materials, moisture retention performance, anticoagulation effect, blood fat regulation effect, immunity enhancement effect, anti-tumor effect and the like. The hygroscopicity and the moisturizing performance of the chitosan quaternary ammonium derivative are researched in the morning (applied chemistry, 1996, 5), fan wood and the like (Wuhan university school news, 2003, 02); the water-soluble hydroxypropyl trimethyl ammonium chloride chitosan (HACC) is prepared by a heterogeneous method by European Wen bamboo and the like (the report of Hunan Tan university college of academic, 2004: 04), and the application performance of the material in fabric softening treatment is researched; the results of blood lipid regulation research of chitosan quaternary ammonium salt carried out by Tiandefeng, etc. (China Biochemical medicine journal, 2002, volume 23, stage 6) show that the chitosan quaternary ammonium salt can obviously reduce TC, TG and LDL-C levels (P is less than 0.01); the Awie F.Kotz et al research compares the permeability of chitosan and chitosan quaternary ammonium salt in intestinal cell membranes; zhang Jian et al (China journal of Biochemical medicine, 2005, volume 26, phase 2) studied the effect of low molecular chitosan quaternary ammonium salt on S180 of mice and the immune function of organisms, and the results showed that the low molecular chitosan quaternary ammonium salt can enhance the immune function of organisms and has the effect of tumor inhibition. Viviane a.spinelli, mauro c.m. Laranjeira and Valfredo t.f. vera (Functional Polymers,2004, 61 (3), 347-352) investigated the adsorption equilibrium of chitosan quaternary ammonium salts to chromium; using trimethylamine, epichlorohydrin and chitosan as raw materials to synthesize N-chitosan quaternary ammonium salt, and preparing a novel organosilicon softening agent. However, no reports on the absorption experiment of the chitin and derivatives thereof on the uric acid exist so far, and no examples of the application of the chitin and derivatives thereof in preventing and treating gout and hyperuricemia are found.
Disclosure of Invention
The invention aims to provide a novel medicine for preventing and treating gout and hyperuricemia.
The medicine for preventing and treating gout and hyperuricemia of the invention comprises: a compound selected from compounds whose structural units satisfy the structural formula (I),
wherein R is 0 Selected from hydrogen atoms, quaternary ammonium chloride ions represented by the structural formula (II);
r' is selected from hydrogen atom, acetyl and quaternary ammonium chloride ions with the structural formula shown as (II);
R、R 1 、R 3 selected from C 1 -C 3 Alkyl of R, R 1 、R 3 Which may be identical or different, R 2 Selected from hydroxy substituted propyl;
in a preferred embodiment of the present invention, the medicament of the present invention comprises chitin and/or a compound selected from quaternary ammonium salt derivatives of chitin, wherein the structural unit of the chitin is represented by structural formula (I), and R' is acetyl; wherein R and R 1 、R 3 Selected from C 1 -C 3 Alkyl radicals of (2), e.g. methyl, ethyl, propyl, R 2 Is a hydroxy-substituted propyl group, preferably a 2-hydroxy-n-propyl group; and the substitution degree of the chitin quaternary ammonium salt derivative is 10-100%. More preferably, the medicament of the invention comprises chitin or O-hydroxypropyl trimethyl ammonium chloride chitin, wherein the O-hydroxypropyl trimethyl ammonium chloride chitinThe degree of substitution of the trimethyl ammonium chloride chitin is 10-100%.
In another preferred embodiment of the present invention, the drug of the present invention comprises a chitosan quaternary ammonium salt derivative, and the chitosan quaternary ammonium salt derivative comprises
The structural unit is shown as a structural formula (I), R 0 N-chitosan quaternary ammonium salt which is hydrogen atom and R' is quaternary ammonium chloride ion shown as a structural formula (II);
the structural unit is shown as a structural formula (I), R 0 Is quaternary ammonium chloride ion with the structural formula shown as (II), and R' is O-chitosan quaternary ammonium salt of hydrogen atom;
and the structural unit is shown as the structural formula (I), R 0 R' is N, O-chitosan quaternary ammonium salt of quaternary ammonium chloride ions with a structural formula shown as (II); wherein the O-chitosan quaternary ammonium salt and the N-chitosan quaternary ammonium saltThe quaternary ammonium ions in the salt and the N, O-chitosan quaternary ammonium salt are selected from the same quaternary ammonium ions shown in the structural formula (II); and R, R 1 、R 3 Selected from C 1 -C 3 Alkyl of (2), e.g. methyl, ethyl, propyl, R 2 Is a hydroxy-substituted propyl group, preferably a 2-hydroxy-n-propyl group.
That is, the O-substituted, N, O-disubstituted quaternary ammonium salt of chitosan contained in the same quaternary ammonium salt of chitosan in the drug is obtained by substituting chitosan with the same quaternary ammonium ion.
More preferably, the chitosan quaternary ammonium salt derivative in the medicament of the invention is hydroxypropyl trimethyl ammonium chloride chitosan, which comprises O-hydroxypropyl trimethyl ammonium chloride chitosan, N-hydroxypropyl trimethyl ammonium chloride chitosan and N, O-hydroxypropyl trimethyl ammonium chloride chitosan;
wherein, the substitution degree of the O-hydroxypropyl trimethyl ammonium chloride chitosan and the N-hydroxypropyl trimethyl ammonium chloride chitosan is 10-100%; the substitution degree of the N, O-hydroxypropyl trimethyl ammonium chloride chitosan is 10-200%.
In a preferred embodiment of the present invention, the drug of the present invention comprises one selected from the group consisting of chitin, hydroxypropyltrimethylammonium chloride chitin and hydroxypropyltrimethylammonium chloride chitosan.
The substitution Degree (DS) of the chitosan quaternary ammonium salt or the chitin quaternary ammonium salt included in the medicine is determined according to the following method: accurately weighing purified sample, dissolving with distilled water, and adding AgNO 3 Titration of Cl in a sample with a standard solution - And calculating the degree of substitution using the formula:
v-consuming AgNO 3 Volume, mL;
M-AgNO 3 molar concentration, mol. L -1 ；
W is sample weight g;
161-unit chitosan molecular weight;
314 is the molecular weight of the unit chitosan quaternary ammonium salt.
In the practice of the pharmaceutical of the present invention, the preferred dosage form is a tablet or capsule.
The medicament of the invention can also contain auxiliary agents, such as excipients and the like, which are required by the preparation of the dosage form in the prior art.
In a preferred embodiment of the invention, the medicament of the invention is prepared by reacting chitin or chitosan with 2, 3-epoxypropyltrialkyl ammonium chloride. In specific implementation, a commercially available chitin or chitosan product can be directly used, and the chitin or chitosan can also be prepared by using the steps (1) and (2) in the following method.
Preferably, it is prepared by a method comprising the following steps:
(1) Cleaning shrimp shell or crab shell, acid decalcifying, removing protein with alkali, washing with water, drying, and pulverizing to obtain chitin;
(2) Deacetylating the chitin obtained in step (1) with 40-50% NaOH to obtain chitosan;
(3) Adding the chitin obtained in the step (1) or the chitosan obtained in the step (2) and an organic alcohol solvent into a three-neck flask, heating in water bath, heating to 80-90 ℃ under stirring, adding a quaternary ammonium salt aqueous solution shown in a structural formula (II), stirring at constant temperature for reacting for 8-24 hours, and filtering, washing, filtering and drying a reaction product to obtain a compound contained in the medicine;
(4) And (2) preparing the chitin obtained in the step (1) or the compound obtained in the step (3) into capsules, or adding a small amount of excipients and pressing into tablets to prepare the medicament.
The invention also provides a preparation method of the medicine.
The medicine of the invention can be prepared by adopting the method for preparing chitin, chitin quaternary ammonium salt and chitosan quaternary ammonium salt in the prior art. Preferably, the method provided by the invention is adopted, and natural product chitin extracted from shrimp and crab shells is used as a raw material, or O-hydroxypropyl trimethyl ammonium chloride chitin, N-hydroxypropyl trimethyl ammonium chloride chitosan or N, O-hydroxypropyl trimethyl ammonium chloride chitosan is prepared by chemical modification.
Specifically, the preparation method of the medicine for preventing and treating gout and hyperuricemia comprises the following steps:
(1) Cleaning shrimp shell or crab shell, acid decalcifying, alkali deproteinizing, washing with water, drying, and pulverizing to obtain chitin;
(2) Deacetylating the chitin obtained in step (1) with 40-50% (v/v) NaOH to obtain chitosan;
(3) Adding the chitin obtained in the step (1) or the chitosan obtained in the step (2) and an organic alcohol solvent into a three-neck flask, heating in water bath, heating to 80-90 ℃ under stirring, adding a 2, 3-epoxypropyltrimonium chloride aqueous solution, stirring at constant temperature for reacting for 8-24 h, and filtering, washing, leaching and drying a reaction product to obtain a compound contained in the medicine;
(4) And (3) preparing the chitin obtained in the step (1) or the compound obtained in the step (3) into capsules, or adding a small amount of excipients into the capsules to be pressed into tablets, thus preparing the medicament.
In the step (1), decalcifying with 4-8% hydrochloric acid, washing with water, and removing protein with 10% NaOH;
in the step (3), isopropanol is used as a solvent, and 2, 3-epoxypropyltrimethylammonium chloride aqueous solution is used as a quaternary ammonium salt aqueous solution to obtain O-hydroxypropyltrimethylammonium chloride chitin and hydroxypropyltrimethylammonium chloride chitosan containing N-hydroxypropyltrimethylammonium chloride chitosan, O-hydroxypropyltrimethylammonium chloride chitosan and N, O-dihydroxypropyltrimethylammonium chloride chitosan.
Wherein, the step (1) or (2) is not necessary, and the step (3) or (4) can be directly carried out by using the commercial chitin or chitosan to prepare the medicament of the invention.
The invention also provides application of the medicament for preventing and treating gout and hyperuricemia in preventing and treating gout or hyperuricemia. Specifically, the invention provides novel applications of chitin, chitin quaternary ammonium salt and chitosan quaternary ammonium salt in preventing and treating gout or hyperuricemia.
The medicament of the invention is subjected to an in vitro simulated uric acid adsorption test under the conditions of simulating the temperature of a human body and the gastrointestinal motility of the human body; animal tests were also performed on the drug of the invention; the result proves that the medicine of the invention has the dual functions of inhibiting uric acid and discharging uric acid.
No significant toxicity was found for the drug of the present invention.
The medicine for preventing and treating gout and hyperuricemia has the advantages that: the medicine of the invention is prepared by taking natural product chitin extracted from shrimp and crab shells as a main raw material through chemical modification, has no toxic or side effect on human bodies, and has safety.
Drawings
Fig. 1 and 2 are infrared spectrograms of the drug of the present invention.
Wherein, curve a in fig. 1 is an infrared spectrogram of chitosan CTS, curve b is an infrared spectrogram of chitosan quaternary ammonium salt CTSJ obtained in example 3 of the present invention; in fig. 2, the curve c is an infrared spectrum of chitin CT, and the curve d is an infrared spectrum of chitin quaternary ammonium salt CTJ obtained in example 2 of the present invention.
The drugs to be analyzed are respectively mixed with kBr and tabletted to carry out infrared spectrum analysis, and an analysis instrument is Tensor27.
Comparing the two curves a and b, the curve a is 1031cm -1 ，1080cm -1 The C-O stretching vibration absorption peak of the primary and secondary alcohol hydroxyl groups is reduced in the infrared spectrum of the b curve, which is probably due to C 6 The primary alcohol-OH on the quaternary ammonium salt of the chitosan is subjected to certain substitution reaction (Lin Yoghurt, synthetic chemistry, 2000, volume 8, no. 2); 1483cm in the b-curve -1 And 3018cm -1 New absorption peaks appear at the parts, which are respectively-CH of quaternary ammonium groups 3 The deformation vibration peak and the stretching vibration peak indicate that the hydroxyl and the amino in the chitosan molecule have nucleophilic substitution reaction to generate the N and O substituted chitosan quaternary ammonium salt.
Comparing the two curves c and d, the typical difference is: (1) 1031cm in c infrared spectrogram -1 ，1080cm -1 The primary and secondary alcohol hydroxyl C-O stretching vibration absorption peak of (2) is reduced in d, which may be C 6 The primary alcohol-OH generates substitution reaction to generate O-chitin quaternary ammonium salt (gao shou, functional polymer bulletin, 2004, volume 17, phase 1); (2) The curve c no longer shows the amino N-H deformation vibration peak (1560 cm) -1 ) And at 1482cm -1 The new absorption peak of deformation vibration of-CH of quaternary ammonium group appears, which shows that the hydroxyl in chitin molecule has nucleophilic substitution reaction to generate chitin quaternary ammonium salt.
Detailed Description
Example 1
Cleaning shrimp shell or crab shell, soaking in 10 times of 4-8% hydrochloric acid solution at room temperature for 24 hr to decalcify. The acid solution was decanted, washed with water to neutrality, and boiled with 10-fold amount of 10% NaOH for 6-8 h to remove the protein therein. Pouring out the alkaline solution, washing to be neutral, soaking for 1h by using 5g/L KMnO4, filtering, washing, stirring and decoloring by using 10g/L oxalic acid aqueous solution at 60-70 ℃, washing to be neutral, drying, crushing to prepare chitin, adding a proper amount of excipient and pressing into tablets.
Example 2
Crushing chitin (commercial, white and flaky, 6.2-6.9% of nitrogen content and less than 1.0% of ash content) to 80-100 meshes, weighing 10g of chitin, placing the chitin into a three-neck flask, adding 90ml of isopropanol, heating to 60 ℃ under stirring, adding 90ml of 50% 2, 3-epoxypropyltrimethylammonium chloride aqueous solution, heating to 80-85 ℃, stirring at constant temperature for 18h, standing overnight, pouring out supernatant, washing and precipitating for 3 times with 100ml of 85% isopropanol, washing for 2 times with a small amount of isopropanol, and drying at 80 ℃ to obtain the O-hydroxypropyltrimethylammonium chloride chitin of the invention, and preparing capsules.
Example 3
Boiling the chitin prepared in example 1 with 10 times of 40-50% NaOH solution for 4h, decanting the alkali solution, washing with water to neutrality, drying, and pulverizing to obtain chitosan; the physical parameters are as follows:
appearance: a white powder; ash (%): less than 1.5; moisture content: 10 percent; degree of deacetylation (%): 80 to 95 percent; viscosity (mPa · s): middle (100-800)
Then weighing 5g of chitosan, placing the chitosan in a three-neck flask, adding 45ml of isopropanol, heating in a water bath, heating to 60 ℃ under stirring, adding 36ml of 50% 2, 3-epoxypropyltrimethylammonium chloride aqueous solution, heating to 80-85 ℃, stirring at constant temperature for reaction for 12h, standing overnight, pouring out supernatant, washing and precipitating for 3 times with 50ml of 85% isopropanol, washing for 2 times with a small amount of isopropanol, drying at 80 ℃ to obtain hydroxypropyl trimethyl ammonium chloride chitosan, adding a small amount of excipient, and pressing into tablets to obtain the medicine.
Example 4
The experiment of in vitro simulated uric acid adsorption of the chitin, chitin quaternary ammonium salt and chitosan quaternary ammonium salt-containing medicament obtained in example 1-3 was carried out under the conditions of simulated human body temperature and human body gastrointestinal motility, and the test method and the results are as follows:
(1) Method for producing a composite material
Taking 30ml of prepared uric acid test solution with a certain concentration, putting the uric acid test solution into a triangular flask with a plug, adding a certain amount of chitin or a derivative thereof, putting the mixture into a TZ-2DH constant-temperature shaking incubator, controlling the temperature to be 36.5-37.0 ℃, shaking at 120 r/min for 6 hours, taking out the triangular flask, filtering the test solution into a colorimetric tube with the plug, measuring the content of uric acid in the solution by using a daily-produced 7060 full-automatic biochemical analyzer, repeating each sample for 2 times, and calculating the adsorption rate of the uric acid by using different doses of medicaments according to the following formula:
(2) As a result, the
The results are shown in Table 1. As can be seen from Table 1, chitin quaternary ammonium salt and chitosan quaternary ammonium salt have strong adsorption capacity to the uric acid, and especially, the addition of 0.06g of the chitosan quaternary ammonium salt can adsorb 97% of the uric acid in the solution.
TABLE 1 test results of uric acid adsorption of the drugs of the present invention
| Test No. | Name of medicine | Medicine quantity (g) | Adsorption Rate (%) |
| 0 1 2 3 4 5 6 7 8 9 10 11 | Blank space
Chitin
Chitin quaternary ammonium salt
Chitin quaternary ammonium salt
Chitin quaternary ammonium salt
Chitin quaternary ammonium salt
Chitin quaternary ammonium salt
Chitin quaternary ammonium salt
Quaternary ammonium salt of chitosan
Quaternary ammonium salt of chitosan
Quaternary ammonium salt of chitosan
Quaternary ammonium salt of |
0 0.75 0.1 0.2 0.3 0.4 0.5 0.75 0.02 0.04 0.06 0.1 | 0 18.3 22.6 36.4 47.7 54.3 60.3 69.7 50.8 91.4 97.9 97.0 |
Example 5
The drug obtained in example 3 of the present invention was used to perform animal uric acid excretion test and uric acid production inhibition test. The test method is as follows:
(1) Test animals: 56 first-class Kunming mice, male, with a weight of 25-28 g, were provided by the Chinese institute of medicine. Animals were randomly divided into five groups, 10 in the normal control group, 16 in the model control group, and 10 in each of the high, medium and low dose groups.
(2) Test formulations: white or light yellow powder, which is dissolved in distilled water and divided into three doses of low, medium and high for standby.
Low dose: preparing 5mg/ml solution with distilled water, and feeding 0.2ml/10g body weight (100 mg/kg);
the medium dosage is as follows: preparing 10mg/ml solution with distilled water, and feeding 0.2ml/10g body weight (100 mg/kg);
high dose: preparing 20mg/ml solution with distilled water, and feeding 0.2ml/10g body weight (100 mg/kg);
the preparation method of the uric acid comprises the following steps: 800mg of uric acid is weighed and ground by 0.75% carboxymethyl cellulose to prepare 40mg/ml and 20mg/ml suspension.
Hypoxanthine preparation method (1000 mg/kg): weighing 1.25g of hypoxanthine, dissolving with 0.5% NaOH, and adjusting pH to 6.0 with 1N HCl.
(3) The modeling test method with uric acid: the control group of the model and the normal control group were injected with distilled water in the abdominal cavity, and the test group was administered by intraperitoneal injection for three days. The model control group and the test group were injected intraperitoneally with 0.75% carboxymethylcellulose urea suspension (0.2 ml/10 gB.W) at the same time of the fourth administration, and 2h after molding, orbital vein blood was collected and the uric acid content in blood was determined.
(4) The method for modeling by hypoxanthine comprises the following steps: the model control group and the normal control group were injected with distilled water in the abdominal cavity, and the test group was administered with drug by intraperitoneal injection for three days. The fourth administration was performed while hypoxanthine (0.2 ml/10 gB.W) was intraperitoneally injected into the model control group and the test group, and 2h after modeling, orbital vein blood was collected and the uric acid content in blood was measured.
(5) And (3) test results:
with hypoxanthine modeling, it can be seen from the results in Table 2 that the model is established (p < 0.01), and uric acid in blood is significantly reduced in the high-dose group (p < 0.05) compared to the model control group.
The results in Table 3 show that the model is established (p < 0.01) by the uric acid modeling test method, and the uric acid in blood is obviously reduced (p < 0.05) in the medium-dose group and the high-dose group compared with the model control group.
TABLE 2 Effect of the drugs of the present invention on blood uric acid of test animals (hypoxanthine modeling method)
| Item | Normal control group | Model control group | Middle dose 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 |
* Represents that P (T test) < 0.05 compared with the model control group
TABLE 3 Effect of the drugs of the present invention on blood uric acid of test animals
| Item | Normal control group | Model control group | Low dose group | Middle dose group | High dose group |
| Blood uric acid (mmol/L) | 0.23 8±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 |
Experiments prove that the medicament has dual effects of inhibiting uric acid and discharging uric acid.
Claims (11)
1. A medicament for preventing and treating gout and hyperuricemia, characterized in that the medicament comprises a compound selected from the group consisting of compounds having a structural unit satisfying the structural formula (I),
wherein R is 0 Selected from hydrogen atoms, quaternary ammonium chloride ions represented by the structural formula (II);
r' is selected from hydrogen atom, acetyl and quaternary ammonium chloride ions with the structural formula shown as (II);
R、R 1 、R 3 selected from C 1 -C 3 Alkyl of R, R 1 、R 3 Which may be identical or different, R 2 Is a hydroxy-substituted propyl group.
2. The medicament according to claim 1, characterized in that the medicament comprises a compound selected from the group consisting of chitin or chitin quaternary ammonium salt derivatives having a structural unit represented by the formula (I) wherein R' is acetyl; wherein R and R 1 、R 3 Is methyl, ethyl or propyl, R 2 Is a hydroxy-substituted propyl group;
the substitution degree of the chitin quaternary ammonium salt derivative is 10-100%.
3. The medicament of claim 2, wherein the medicament comprises chitin or O-hydroxypropyltrimethylammonium chloride chitin, wherein the degree of substitution of the O-hydroxypropyltrimethylammonium chloride chitin is 10 to 100%.
4. The medicament of claim 1, wherein the medicament comprises a chitosan quaternary ammonium salt derivative comprising
The structural unit is shown as a structural formula (I), R 0 N-chitosan quaternary ammonium salt which is hydrogen atom and R' is quaternary ammonium chloride ion shown in a structural formula (II);
the structural unit is shown as a structural formula (I), R 0 Is quaternary ammonium chloride ion with the structural formula shown as (II), and R' is O-chitosan quaternary ammonium salt of hydrogen atom;
and the structural unit is shown as the structural formula (I), R 0 R' is N, O-chitosan quaternary ammonium salt of quaternary ammonium chloride ions with a structural formula shown as (II);
wherein the quaternary ammonium ions in the O-chitosan quaternary ammonium salt, the N-chitosan quaternary ammonium salt and the N, O-chitosan quaternary ammonium salt are selected from the same quaternary ammonium ions with the structural formula shown in (II); and R, R 1 、R 3 Is methyl, ethyl or propyl, R 2 Is a hydroxy-substituted propyl group.
5. The pharmaceutical according to claim 4, wherein the chitosan quaternary ammonium salt derivative is hydroxypropyl trimethyl ammonium chloride chitosan comprising O-hydroxypropyl trimethyl ammonium chloride chitosan, N-hydroxypropyl trimethyl ammonium chloride chitosan and N, O-hydroxypropyl trimethyl ammonium chloride chitosan;
wherein, the substitution degree of the O-hydroxypropyl trimethyl ammonium chloride chitosan and the N-hydroxypropyl trimethyl ammonium chloride chitosan is 10-100 percent;
the substitution degree of the N, O-hydroxypropyl trimethyl ammonium chloride chitosan is 10-200%.
6. Pharmaceutical according to any one of claims 1 to 5, characterized in that the pharmaceutical is in the form of a tablet or capsule.
7. The medicament according to any one of claims 1 to 5, wherein said medicament is prepared by reacting chitin or chitosan with 2, 3-epoxypropyltrialkyl ammonium chloride.
8. The medicament according to claim 7, characterized in that it is prepared by a process comprising the following steps:
(1) Cleaning shrimp shell or crab shell, acid decalcifying, alkali deproteinizing, washing with water, drying, and pulverizing to obtain chitin;
(2) Deacetylating the chitin obtained in step (1) with 40-50% NaOH to obtain chitosan;
(3) Adding the chitin obtained in the step (1) or the chitosan obtained in the step (2) and an organic alcohol solvent into a three-neck flask, heating in water bath, heating to 80-90 ℃ under stirring, adding a 2, 3-epoxypropyltrialkyl ammonium chloride aqueous solution, stirring at a constant temperature for reacting for 8-24 hours, and filtering, washing, leaching and drying a reaction product to obtain a compound contained in the medicine;
(4) And (3) preparing the chitin obtained in the step (1) or the compound obtained in the step (3) into capsules, or adding a small amount of excipients into the capsules to be pressed into tablets, thus preparing the medicament.
9. The method for preparing the medicament for preventing and treating gout and hyperuricemia according to any one of claims 1 to 8, comprising the steps of:
(1) Cleaning shrimp shell or crab shell, acid decalcifying, alkali deproteinizing, washing with water, drying, and pulverizing to obtain chitin;
(2) Deacetylating the chitin obtained in step (1) with 40-50% (v/v) NaOH to obtain chitosan;
(3) Adding the chitin obtained in the step (1) or the chitosan obtained in the step (2) and an organic alcohol solvent into a three-neck flask, heating in water bath, heating to 80-90 ℃ under stirring, adding a 2, 3-epoxypropyltrialkyl ammonium chloride aqueous solution, stirring at constant temperature for reacting for 8-24 hours, and filtering, washing, filtering and drying a reaction product to obtain a compound contained in the medicine;
(4) And (3) preparing the chitin obtained in the step (1) or the compound obtained in the step (3) into capsules, or adding a small amount of excipients into the capsules to be pressed into tablets, thus preparing the medicament.
10. The method according to claim 9, wherein the reaction mixture is heated to a temperature in the reaction mixture
In the step (1), decalcifying with 4-8% hydrochloric acid, washing with water, and removing protein with 10% NaOH;
in the step (3), isopropanol is used as a solvent, and 2, 3-epoxypropyltrimethylammonium chloride aqueous solution is used as a quaternary ammonium salt aqueous solution to obtain O-hydroxypropyltrimethylammonium chloride chitin and hydroxypropyltrimethylammonium chloride chitosan containing N-hydroxypropyltrimethylammonium chloride chitosan, O-hydroxypropyltrimethylammonium chloride chitosan and N, O-hydroxypropyltrimethylammonium chloride chitosan.
11. The use of the agent for the prophylaxis and treatment of gout and hyperuricemia according to any one of claims 1 to 8, in the prophylaxis and treatment of gout or hyperuricemia.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101972489A (en) * | 2010-09-30 | 2011-02-16 | 吴奕光 | Novel wound self-healing biological material, preparation method and application thereof |
| CN101869552B (en) * | 2009-04-25 | 2012-01-25 | 青岛科技大学 | Preparation method of chitin tablet |
| CN103665187A (en) * | 2013-11-22 | 2014-03-26 | 徐广苓 | Preparation method for chitosan |
| CN105456289A (en) * | 2015-12-08 | 2016-04-06 | 杜玉茗 | Composite western medicine formula for treating gout |
| CN114259507A (en) * | 2021-12-27 | 2022-04-01 | 暨南大学 | Application of Klebsiella minutissima in preparing medicine for treating and/or preventing hyperuricemia-related diseases |
-
2006
- 2006-07-13 CN CN2006100910892A patent/CN101103994B/en active Active
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101869552B (en) * | 2009-04-25 | 2012-01-25 | 青岛科技大学 | Preparation method of chitin tablet |
| CN101972489A (en) * | 2010-09-30 | 2011-02-16 | 吴奕光 | Novel wound self-healing biological material, preparation method and application thereof |
| CN103665187A (en) * | 2013-11-22 | 2014-03-26 | 徐广苓 | Preparation method for chitosan |
| CN105456289A (en) * | 2015-12-08 | 2016-04-06 | 杜玉茗 | Composite western medicine formula for treating gout |
| CN114259507A (en) * | 2021-12-27 | 2022-04-01 | 暨南大学 | Application of Klebsiella minutissima in preparing medicine for treating and/or preventing hyperuricemia-related diseases |
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| Publication number | Publication date |
|---|---|
| CN101103994B (en) | 2010-08-18 |
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