CN108524518A - A kind of antigout effect of tetrazole compound - Google Patents
A kind of antigout effect of tetrazole compound Download PDFInfo
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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Abstract
The invention discloses a kind of effects of the antigout of tetrazole compound, invention increases the clinical indication of tetrazole compound, it are made to cannot be only used for treatment epilepsy etc., can be used for treatment hyperuricemia, gout.By tetrazole compound preparation by drug administration by injection, making hyperuricemia model to mouse Monosodium urate has apparent effect, and is higher than Allopurinol positive controls.Tetrazole compound small toxicity, few side effects, while tool is significantly reduced blood uric acid levels, antigout effect, can prepare the preparation of ideal treatment gout.
Description
Technical field
The present invention relates to antigout compound fields, are acted on more particularly, to a kind of antigout of tetrazole compound.
Technical background
Gout (metabolic arthritis) is a kind of because of disorders of purine metabolism, make uric acid accumulate caused by disease,
Belong to arthritic one kind, also known as metabolic arthritis.Clinical signs are hyperuricemia, gouty acute arthritis, pain
Wind stone deposition, characteristic chornic arthritis and arthritis deformans, often involve kidney, cause arteriosclerotic kidney and kidney uric acid knot
Stone.Epidemiology shows that the illness rate of European and American areas gout is 0.2~1.7%.In China, the incidence of gout is presented in recent years
The trend of liter, China's general population's illness rate about 1.14%.The gout incidence of China areas of well-being is apparently higher than rural area.Gout is
Through the quality of life for having seriously affected patient.Currently, clinically the current kind of antigout gout suppressant is few, western medical treatment gout
Drug mainly have colchicin, non-steroidal anti-inflammatory drugs, glucocorticoid, cortex hormone of aadrenaline, Glucosamine, IL inhibit
Agent.These drugs are all defective in the treatment.Weak curative effect, side effect become greatly the bottleneck of its clinical application.
Invention content
The purpose of the present invention is to provide a kind of effect of the antigout of tetrazole compound, tetrazole compound can have
The treatment uric acid of effect produces gout caused by the hyperuricemia and hyperuricemia of hyperfunction type, using tetrazole compound system
Hyperuricemia, goat are treated in agent, have the function of reducing uric acid in blood level, with obvious effects, toxicity is low, can give for a long time
Medicine.
The present invention is directed to the problem of being mentioned in background technology, and the technical solution taken is：A kind of tetrazole compound
Antigout acts on, and tetrazole compound is 1,2,3,4- tetrazole compounds of the expression of general formula 1,2,3, its hydration
Object or its salt.
In above-mentioned formula, R1, R2 indicate ortho position, meta position, the amino of contraposition, fluorine, chlorine, bromine, sulfydryl, cyano；R3 indicates substituent group
Can be substitution or unsubstituting biocides base or the corresponding pyridine N-oxides base of these pyridyl groups of halogen, cyano or phenyl,
Or the substituted-phenyl with cyano, nitro substituent, or also there is substitution or unsubstituted low other than the cyano, nitro
Grade alkoxy, N- low alkyl groups substituted piperazinyl or high piperazine base, lower alkyl sulfur groups, phenylsulfartyl or low-grade alkyl amino are made
For the substituted-phenyl of substituent group；R4 indicate hydrogen, new pentane acyloxy replace low alkyl group, with 1,2,3,4- shown in general formula (3)
One of tetrazole ring nitrogen is bonded.
This tetrazole compound can prepare the pharmaceutical dosage form for treating gout.
This tetrazole compound can prepare the pharmaceutical dosage form for treating hyperuricemia.
1,2,3,4- tetrazole compounds, its hydrate or its salt pref that general formula 1,2,3 indicates can be prepared individually
Treat the drug of gout.
Gout is, due to various reasons caused by gout.
This tetrazole compound preparation includes oral preparation, and oral preparation includes tablet and capsule.
This tetrazole compound preparation includes injection, and injection includes powder ampoule agent for injection and injection.
This tetrazole preparation includes all organic acids and inorganic acid that 1,2,3 compound of general formula can receive into salt.
Preferably, the preparation method that tetrazole compound is used to prepare compound oral soft capsule preparation includes：It carries
It takes, prepares extract powder, prepares soft capsule, specifically include following steps：
Extraction：The same batch irexis sonchifolias of 100g are taken, 12~15 times of amount water are added, in 0.07~0.08MPa, 85~88 DEG C of items
It is decocted under part 45~60 minutes, 8~10 times of amount water is then added and under equal conditions decoct 45~60 minutes, collecting decoction subtracts
Pressure is concentrated into 150~180g, lets cool to 37~39 DEG C, for use；Decompression extraction operation is simple, and method is feasible, to irexis sonchifolia
The yield of adenosine in active ingredient can be significantly improved by carrying out decompression extraction, prevent the degradation of adenosine, while again will not be to medicinal extract
And the yield of general flavone has an impact in active ingredient；
Prepare extract powder：New calcium oxide breast is added into decocting liquid under stiring and adjusts pH value to 9.8~10.0, it is small to place 10~15
When, sediment is suspended in 6~8 times of 85~95% ethanol solutions of amount by centrifugation, and pH value is adjusted to 3.3~3.5 with sulfuric acid solution,
Being sufficiently stirred makes that the reaction was complete, centrifugation, and centrifugate adds sodium hydroxide solution to adjust pH value to 6.8~7.0, filtering, filtrate decompression
Ethyl alcohol is recycled, and waves most ethyl alcohol, the medicinal extract of relative density 1.1~1.12 is concentrated under the conditions of 60~62 DEG C, then low temperature drying
And crush to obtain sowthistle-leaf ixeris seedling extract powder, sowthistle-leaf ixeris seedling extract powder is placed in airslide disintegrating mill, stream pressure be 750~850kPa,
Charging rate carries out ultramicro grinding under conditions of being 160~200r/min, obtains sowthistle-leaf ixeris seedling medicinal extract Ultramicro-powder；By extract powder Ultramicro-powder
Soft capsule is prepared after broken, not only active ingredient dissolution rate increases, but also mobility of particle is improved, and capsule charge loading amount is stablized
And production efficiency is high, the mucilaginous substance after processing in pulvis can be greatly reduced, and deal with relatively easily, be conducive to mitigate production people
The labor intensity of member, while ethyl alcohol can reduce production cost with recycling；
Prepare soft capsule：422~425 portions of soybean oils, 28~30 parts of beeswaxs, 5.5~5.6 parts of span-80 mixings are taken, are heated to 68
~70 DEG C make beeswax melt completely, and stirring is cooled to 33~35 DEG C, be added 80~110 parts of sowthistle-leaf ixeris seedling medicinal extract Ultramicro-powders, 0.2~
0.21 part of tetrazole, stirs evenly, and vacuumizes cancellation bubble, spare；Take gelatin, glycerine, water according to 1:0.4~0.5:0.8~
Water-bath type glue tank is added in 1.0 ratio, and 1~1.5 hour is kept the temperature after stirring and melting, and vacuumizes cancellation bubble, crosses 80~120
Mesh screen is placed in 60~63 DEG C of glue bucket heat preservations, stands 2~4 hours；In the environment of 18~26 DEG C, relative humidity are 40~45%
With soft capsule press, above-mentioned material is inserted, soft capsule is suppressed；It is done in the environment of 24~25 DEG C, relative humidity 25~30%
Dry 16~24 hours to get tetrazole soft capsule preparation；Tetrazole soft capsule preparation prescription rationally, feasible process, content is
The sticky colloid of taupe, gas is micro-, bitter, the dosage form is high with bioavilability, toxic side effect is small, absorption is rapid, stability is good,
The advantages that convenient for taking, the effective effectiveness ingredient of soft capsule such as tetrazole and adenosine class, flavonoids, the sesquialter in sowthistle-leaf ixeris seedling extract powder
The dissolution rate of terpene lactones, terpene and sterols etc. is higher, is conducive to the rapid absorption of body.
Preferably, preparing in extract powder step, 1.2~1.5% n-butanol and 0.3 is contained in 85~95% ethanol solutions
~0.4 ‰ 4- benzyl -2- azolactones, (R) 4- benzyl -2- azolactones containing 6.2-6.4% in 4- benzyl -2- azolactones；Just
Butanol can be acted on 4- benzyl -2- azolactones makes the hydrogen bond base of a fruit of the quaternary structure of protein in irexis sonchifolia join, effectively
Protein degradation matter quaternary structure makes the protein denaturation in irexis sonchifolia, and then it is made to be gathered into protein denaturation gel group,
Meanwhile (R) 4- benzyl -2- azolactones of special proportioning and the synergistic effect of (S) 4- benzyl -2- azolactones can act on albumen
The tie point of the linear peptides interchain of the space structure of qualitative change gel group, to prevent adenosine and Flavonoid substances from entering protein
Denaturant gel group can reduce the probability that adenosine is separated off with Flavonoid substances while denaturation and protein isolate matter,
The content and purity of adenosine in extract powder, terpene, half terpene and Flavonoid substances isoreactivity substance are greatly improved, extract powder is improved
Biological effectiveness.
Compared with the prior art, the advantages of the present invention are as follows：1）Tetrazole compound can effectively treat uric acid production
Gout caused by the hyperuricemia and hyperuricemia of hyperfunction type, using tetrazole compound preparation for treating antihyperuricemic
Disease, goat, have the function of reducing uric acid in blood it is horizontal, it is with obvious effects, toxicity is low, can long term administration；2）Tetrazole is soft
Capsule preparations prescription rationally, feasible process, content be the sticky colloid of taupe, gas is micro-, bitter, the dosage form have biological utilisation
The advantages that degree is high, toxic side effect is small, absorptions is rapid, stability is good, convenient for taking, the effective effectiveness ingredient of soft capsule such as tetrazole and
The dissolution rate of adenosine class, flavonoids, Sesquiterpene lactones, terpene and sterols etc. in sowthistle-leaf ixeris seedling extract powder is higher, is conducive to
The rapid absorption of body.
Specific implementation mode
The present invention program is described further below by embodiment：
Embodiment 1：
The preparation method that tetrazole compound is used to prepare compound oral soft capsule preparation includes the following steps：
1）It takes the same batch irexis sonchifolias of 100g, 12 times of amount water is added, decoct 45 minutes under the conditions of 0.07MPa, 85 DEG C, so
8 times of amount water are added afterwards under equal conditions to decoct 45 minutes, collecting decoction is concentrated under reduced pressure into 150g, lets cool to 37 DEG C, for use；
2）New calcium oxide breast is added into decocting liquid under stiring and adjusts pH value to 9.8, places 10 hours, sediment is suspended in 6 by centrifugation
In times 85% ethanol solution of amount, pH value is adjusted to 3.3 with sulfuric acid solution, being sufficiently stirred makes that the reaction was complete, and centrifugation, centrifugate adds hydrogen
Sodium hydroxide solution adjusts pH value to 6.8, filters, decompression filtrate recycling ethanol, and wave most ethyl alcohol, is concentrated under the conditions of 60 DEG C opposite
Then the medicinal extract of density 1.1 low temperature drying and crushes to obtain sowthistle-leaf ixeris seedling extract powder, sowthistle-leaf ixeris seedling extract powder is placed in airslide disintegrating mill
In, ultramicro grinding is carried out under conditions of stream pressure is 850 kPa, charging rate is 200 r/min, it is super to obtain sowthistle-leaf ixeris seedling medicinal extract
Micro mist；3）422 portions of soybean oils, 28 parts of beeswaxs, 5.5 parts of span-80 mixings are taken, being heated to 68 DEG C makes beeswax melt completely, stirring
33 DEG C are cooled to, 80 parts of sowthistle-leaf ixeris seedling medicinal extract Ultramicro-powders, 0.2 part of tetrazole is added, stirs evenly, vacuumizes cancellation bubble, it is spare；
It takes 1000 parts of gelatin, 400 parts of glycerine, 800 parts of water that water-bath type glue tank is added, keeps the temperature 1 hour after stirring and melting, vacuumize and disappear
Bubble is removed, 80 mesh screens are crossed, 60 DEG C of glue bucket heat preservations is placed in, stands 2 hours；With soft in the environment of 18 DEG C, relative humidity are 40%
Capsule press inserts above-mentioned material, suppresses soft capsule；It is 16 hours dry in the environment of 24 DEG C, relative humidity 25%, i.e.,
Obtain tetrazole soft capsule preparation.
Embodiment 2：
Tetrazole compound is used to prepare compound oral soft capsule preparation, and preparation method specifically includes following steps：
1）It takes the same batch irexis sonchifolias of 100g, 15 times of amount water is added, decoct 60 minutes under the conditions of 0.08MPa, 88 DEG C, so
10 times of amount water are added afterwards under equal conditions to decoct 60 minutes, collecting decoction is concentrated under reduced pressure into 180g, lets cool to 39 DEG C, for use；
Decompression extraction operation is simple, and method is feasible, and the receipts of adenosine in active ingredient can be significantly improved by carrying out decompression extraction to sowthistle-leaf ixeris seedling
Rate prevents the degradation of adenosine, while will not be had an impact again to the yield of general flavone in medicinal extract and active ingredient；
2）Prepare extract powder：New calcium oxide breast is added into decocting liquid under stiring and adjusts pH value to 10, places 15 hours, centrifugation,
Sediment is suspended in 8 times of 95% ethanol solutions of amount, the 4- benzyls containing 1.2% n-butanol and 0.4 ‰ in 95% ethanol solution
Base -2- azolactones adjust pH value containing 6.2% (R) 4- benzyl -2- azolactones in 4- benzyl -2- azolactones with sulfuric acid solution
To 3.5, being sufficiently stirred makes that the reaction was complete, centrifugation, and centrifugate adds sodium hydroxide solution to adjust pH value to 7.0, filtering, filtrate decompression
Ethyl alcohol is recycled, and waves most ethyl alcohol, the medicinal extract that relative density is 1.12 is concentrated under the conditions of 62 DEG C, then low temperature drying and is crushed
Sowthistle-leaf ixeris seedling extract powder is placed in airslide disintegrating mill by sowthistle-leaf ixeris seedling extract powder, stream pressure be 750 kPa, charging rate 160
Ultramicro grinding is carried out under conditions of r/min, obtains sowthistle-leaf ixeris seedling medicinal extract Ultramicro-powder；Soft capsule will be prepared after extract powder ultramicro grinding, no
Only active ingredient dissolution rate increases, and mobility of particle is improved, and capsule charge loading amount is stable and production efficiency is high, processing
The mucilaginous substance in pulvis can be greatly reduced afterwards, deal with the labor intensity for being relatively easily conducive to mitigate producers, simultaneously
Ethyl alcohol can reduce production cost with recycling；
3）Prepare soft capsule：425 portions of soybean oils, 30 parts of beeswaxs, 5.6 parts of span-80 mixings are taken, being heated to 70 DEG C keeps beeswax complete
Melting, stirring are cooled to 35 DEG C, and 110 parts of sowthistle-leaf ixeris seedling medicinal extract Ultramicro-powders, 0.21 part of tetrazole is added, stirs evenly, vacuumizes and disappear
Bubble is removed, it is spare；It takes 1000 parts of gelatin, 500 parts of glycerine, 1000 parts of water that water-bath type glue tank is added, stirs and kept the temperature after melting
1.5 hours, cancellation bubble is vacuumized, crosses 120 mesh screens, 63 DEG C of glue bucket heat preservations is placed in, stands 4 hours；In 26 DEG C, relative humidity
Soft capsule press is used in the environment of being 45%, is inserted above-mentioned material, is suppressed soft capsule；In 25 DEG C, the ring of relative humidity 30%
24 hours are dried under border to get tetrazole soft capsule preparation；Tetrazole soft capsule preparation prescription rationally, feasible process, content
For the sticky colloid of taupe, gas is micro-, bitter, and the dosage form is high with bioavilability, toxic side effect is small, absorption is rapid, stability
The advantages that good, convenient for taking, the effective effectiveness ingredient of soft capsule such as tetrazole in sowthistle-leaf ixeris seedling extract powder adenosine class, flavonoids,
The dissolution rate of Sesquiterpene lactones, terpene and sterols etc. is higher, is conducive to the rapid absorption of body.
Embodiment 3：
The preparation method that tetrazole compound is used to prepare compound oral soft capsule preparation includes：Extract, prepare extract powder,
Soft capsule is prepared, following steps are specifically included：
Extraction：The same batch irexis sonchifolias of 100g are taken, 14 times of amount water are added, 60 points are decocted under the conditions of 0.075MPa, 86 DEG C
Then clock is added 10 times of amount water and under equal conditions decocts 45 minutes, collecting decoction is concentrated under reduced pressure into 150g, lets cool to 38 DEG C,
For use；Decompression extraction operation is simple, and method is feasible, and adenosine in active ingredient can be significantly improved by carrying out decompression extraction to sowthistle-leaf ixeris seedling
Yield, prevent the degradation of adenosine, while will not be had an impact again to the yield of general flavone in medicinal extract and active ingredient；
Prepare extract powder：New calcium oxide breast is added into decocting liquid under stiring and adjusts pH value to 10, places 10 hours, centrifuges, it will
Sediment is suspended in 6 times of 90% ethanol solutions of amount, the 4- benzyls-containing 1.2% n-butanol and 0.3 ‰ in 90% ethanol solution
2- azolactones, containing 6.4% (R) 4- benzyl -2- azolactones in 4- benzyl -2- azolactones, with sulfuric acid solution adjust pH value to
3.3, being sufficiently stirred makes that the reaction was complete, centrifugation, and centrifugate adds sodium hydroxide solution to adjust pH value to 7, filtering, filtrate decompression recycling
Ethyl alcohol, and wave most ethyl alcohol, is concentrated into the medicinal extract of relative density 1.1 under the conditions of 60 DEG C, then low temperature drying and crush to obtain sowthistle-leaf ixeris seedling
Sowthistle-leaf ixeris seedling extract powder is placed in airslide disintegrating mill by extract powder, stream pressure is 800 kPa, charging rate is 180 r/min
Under conditions of carry out ultramicro grinding, obtain sowthistle-leaf ixeris seedling medicinal extract Ultramicro-powder；Soft capsule will be prepared after extract powder ultramicro grinding, not only effectively
Ingredient dissolution rate increases, and mobility of particle is improved, and capsule charge loading amount is stable and production efficiency is high, pulvis after processing
In mucilaginous substance can be greatly reduced, deal with relatively easy, be conducive to the labor intensity for mitigating producers, while ethyl alcohol can
With recycling, production cost is reduced；
Prepare soft capsule：425 portions of soybean oils, 30 parts of beeswaxs, 5.5 parts of span-80 mixings are taken, being heated to 68 DEG C keeps beeswax completely molten
Melt, stirring is cooled to 34 DEG C, and 100 parts of sowthistle-leaf ixeris seedling medicinal extract Ultramicro-powders, 0.2 part of tetrazole is added, stirs evenly, vacuumizes cancellation gas
Bubble, it is spare；It takes 340 parts of hydroxypropyl celluloses, 660 parts of gelatin, 500 parts of glycerine and 1000 parts of water that water-bath type glue tank is added, stirs
1 hour is kept the temperature after mixing and melting, cancellation bubble is vacuumized, sieves with 100 mesh sieve net, 62 DEG C of glue bucket heat preservations is placed in, stands 3 hours；
20 DEG C, relative humidity be 40% in the environment of use soft capsule press, insert above-mentioned material, suppress soft capsule；In 24 DEG C, phase
To dry 20 hours in the environment of humidity 25% to get tetrazole soft capsule preparation；Tetrazole soft capsule preparation prescription rationally, work
Skill is feasible, and content is the sticky colloid of taupe, and gas is micro-, bitter, and the dosage form is high with bioavilability, toxic side effect is small, inhales
Receive the advantages that rapid, stability is good, convenient for taking, the effective effectiveness ingredient of soft capsule such as tetrazole and the gland in sowthistle-leaf ixeris seedling extract powder
The dissolution rate of glycoside, flavonoids, Sesquiterpene lactones, terpene and sterols etc. is higher, is conducive to the rapid absorption of body.
It prepares in soft capsule step, containing 2.8 parts of oleic acid formicester in every 500 parts of glycerine, contains 1.7 in every 1000 parts of water
Part glyceraldehyde, contain 17.5% L- (-)-glyceraldehyde in glyceraldehyde；α chains, β chains and γ chains in gelatin can be in glyceraldehyde
Catalytic action under be crosslinked rapidly, the intersegmental formation covalent cross-linking of longer gelatin chain can be made, so as to effectively improve gelatin
Viscosity, solidification point and gel strength, improve the stability of capsule, extend the pot-life of capsule；Gelatin after crosslinking is glue
Former albumen group, into body after can be denaturalized by hydrochloric acid in gastric juice rapidly, gelatin is decomposed into peptone through pepsin, is further broken into small
Peptide, amino acid are absorbed by organisms utilization；On the other hand, hydrolysis can occur for part oleic acid formicester, generate oleic acid, oleic acid can
To seize the oxidant in system and react, to reduce active ingredient such as sesquiterpene lactone in sowthistle-leaf ixeris seedling extract powder
The oxidation probability of class, half terpene, triterpenes etc. preserves antigout effect of sowthistle-leaf ixeris seedling extract powder；Special proportioning in glyceraldehyde
L- (-)-glyceraldehyde can act synergistically with D- (-)-glyceraldehyde, which can effectively reconcile hydroxypropyl cellulose
Interaction between gelatin is filled up in " gap " between the two, strengthens the mechanical strength and consistency of capsule gel coat, not only
It protects capsule 's content from oxidative degradation, but also the pot-life of capsule can be greatly prolonged, while not influencing glue again
Capsule enters the content dissolution rate after body, from every side the comprehensive quality for improving capsule.
The dissolution in vitro of the soft capsule preparation in embodiment 1,2,3 is measured by simulating gastric environment, measures tetrazole
Opposite dissolution data is as shown in table 1 with sowthistle-leaf ixeris seedling preparation for dissolution rate.
Table 1. simulates the dissolution in vitro of soft capsule preparation in embodiment 1-3 under gastric environment
As can be seen from Table 1, soft capsule preparation has the opposite dissolution rate of higher tetrazole dissolution rate and sowthistle-leaf ixeris seedling preparation, explanation
Soft capsule preparation is higher to the release of content preparation and utilization ratio.
Embodiment 4：
Influence of the tetrazole compound preparation to Studies on Animal Models of Hyperuricemic Mice：
1. animal packet and dosage：By weight 20-25g mouse 60, it is randomly divided into 6 groups, every group 10, i.e. blank control
Group, model group, drug control group（Allopurinol）, antigout injection low, middle and high dose groups.Each group gastric infusion, normal group and
The physiological saline 0.2mL of the capacity such as model group gavage, drug control group Allopurinol 1.875g/mL, medicine group difference is in mass ratio
4.6875%, 9.375%, 18.75%, daily gavage is primary, is 0.2mL, continuous 5 days.
2. modeling method：Its correlation technique is used after reference literature, until the 5th day, after the completion of last gavage, given through 1 hour
Mouse is injected intraperitoneally, and carrying out eyeball to mouse after 1 hour again after the completion of injection takes blood.In addition to blank group, remaining each group
Mouse is injected intraperitoneally with uric acid（500mg/Kg）, induce Gout Model.Blank group injects the physiological saline of isometric(al).
3. sample is collected：After last mouse is administered 1 hour, other than blank group, remaining each group animal intraperitoneal injection
0.0625g/mL uric acid causes chmice acute hyperuricemia.After injection 1 hour, each grouping animal wins eyeball and takes blood,
Blood is set in 5mL biochemistry heparin tubes（Promote solidifying）It is spare.
4. assay method：Blood is placed in a centrifuge and is centrifuged 5 minutes with 3000r/min, supernatant is taken to add No. two reagents
2.0mL mixings, after ten minutes, 3000r/min is centrifuged 5 minutes.Supernatant is taken, adds No. three, No. four each 0.5mL of reagent, mixing is equal
It is even, it measures the absorbance value of each pipe with wavelength 690nm, 1cm optical path, blank tube zeroing after 10 minutes and calculates blood urine
Acid value.
5. result：A kind of administration of tetrazole compound preparation oral is to mouse, the influence of hyperuricemia caused by uric acid
2 are the results are shown in Table, by table result it is found that continuous oral is administered for 5 days, high dose group is to the inhibiting rate of mouse hyperuricemia
75.5%, mouse uric acid inhibiting rate is higher than positive controls, and anti-uric acid activity is better than present clinical application Allopurinol.
The influence of table 2.J4 mouse blood uric acids（`x±s）
Note：Compared with blank group：△ P ＜ 0.01；The * P ＜ 0.01 compared with model group, * * * * P ＜ 0.01.
Routine operation in operating procedure of the present invention is well known to those skilled in the art, herein without repeating.
Technical scheme of the present invention is described in detail in embodiment described above, it should be understood that the above is only
For specific embodiments of the present invention, it is not intended to restrict the invention, all any modifications made in the spirit of the present invention,
Supplement or similar fashion replacement etc., should all be included in the protection scope of the present invention.
Claims (10)
1. a kind of antigout of tetrazole compound acts on, it is characterised in that：The tetrazole compound is in the high urine for the treatment of
Application in acidaemia, goat.
2. a kind of antigout of tetrazole compound according to claim 1 acts on, it is characterised in that：The tetrazole
Class compound is 1,2,3,4- tetrazole compounds, its hydrate or its salt that general formula 1,2,3 indicates：
In above formula, R1, R2 indicate ortho position, meta position, the amino of contraposition, fluorine, chlorine, bromine, sulfydryl, cyano；R3 indicates that substituent group also may be used
To be substitution or unsubstituting biocides base or the corresponding pyridine N-oxides base of these pyridyl groups of halogen, cyano or phenyl, or
It is there is the substituted-phenyl of cyano, nitro substituent, or also there is substitution or unsubstituted rudimentary other than the cyano, nitro
Alkoxy, N- low alkyl groups substituted piperazinyl or high piperazine base, lower alkyl sulfur groups, phenylsulfartyl or low-grade alkyl amino conduct
The substituted-phenyl of substituent group；R4 indicates that hydrogen, new pentane acyloxy replace low alkyl group, with shown in general formula (3) 1,2,3,4- tetra-
One of azoles ring nitrogen is bonded.
3. a kind of antigout of tetrazole compound according to claim 2 acts on, it is characterised in that：The tetrazole
Class preparation includes all organic acids and inorganic acid that 1 compound can receive into salt.
4. a kind of antigout of tetrazole compound according to claim 2 acts on, it is characterised in that：The general formula 1,
2, the 3 1,2,3,4- tetrazole compounds indicated or its hydrate or its salt pref can prepare the system for the treatment of hyperuricemia
Agent.
5. a kind of antigout of tetrazole compound according to claim 2 acts on, it is characterised in that：The general formula 1,
2, the 3 1,2,3,4- tetrazole compounds indicated or its hydrate or its salt pref can prepare the preparation for the treatment of gout.
6. a kind of antigout of tetrazole compound according to claim 5 acts on, it is characterised in that：The gout disease
Disease is the gout caused by due to various reasons.
7. a kind of antigout of tetrazole compound according to claim 4 or 5 acts on, it is characterised in that：Described four
Nitrogen azole compounds preparation includes injection, and the injection includes powder ampoule agent for injection or injection.
8. a kind of antigout of tetrazole compound according to claim 4 or 5 acts on, it is characterised in that：Described four
Nitrogen azole compounds preparation includes oral preparation, and the oral preparation includes tablet or capsule.
9. a kind of antigout of tetrazole compound according to claim 8 acts on, it is characterised in that：The tetrazole
The preparation method that class compound is used to prepare compound oral soft capsule preparation includes the following steps：
Extraction：Irexis sonchifolia is taken, is decocted after water is added, decocting liquid is taken to be concentrated under reduced pressure into, is let cool for use；
Prepare extract powder：Stirring is lower new calcium oxide breast is added into decocting liquid to be adjusted pH value to 9.8~10.0, is centrifuged after standing, heavy
Starch is suspended in 85~95% ethanol solutions containing n-butanol and 4- benzyl -2- azolactones, is adjusted pH to 3.3~3.5, is filled
Point stirring makes that the reaction was complete, and centrifugation, centrifugate is adjusted to neutrality, filters, and filtrate decompression waves to the greatest extent and recycles ethyl alcohol, concentrates as medicinal extract,
Then simultaneously ultramicro grinding obtains sowthistle-leaf ixeris seedling medicinal extract Ultramicro-powder for low temperature drying；
Prepare soft capsule：It takes soybean oil, beeswax, span-80 mixings, heating that beeswax is made to melt completely, is added after stirring is cooling bitter
Plate medicinal extract Ultramicro-powder, tetrazole, stir evenly, and vacuumize cancellation bubble；Gelatin, glycerine, water is taken to stir and kept the temperature after melting,
Cancellation bubble is vacuumized, keeps the temperature and stands after sieving；Above-mentioned material is inserted into soft capsule press, is suppressed and dry that tetrazole is soft
Capsule preparations.
10. a kind of antigout of tetrazole compound according to claim 9 acts on, it is characterised in that：Four nitrogen
Azole compounds are used to prepare in the preparation method of compound oral soft capsule preparation, prepare the ethanol solution during extract powder
In the 4- benzyl -2- azolactones containing 1.2~1.5% n-butanol and 0.3~0.4 ‰, contain 6.2 in 4- benzyl -2- azolactones
~6.4% (R) -4- benzyl -2- azolactones.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115232086A (en) * | 2022-07-19 | 2022-10-25 | 扬州市普林斯医药科技有限公司 | Preparation method of 4-benzyl-2 (3H) -oxazolone |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106032377A (en) * | 2015-03-12 | 2016-10-19 | 天津药物研究院有限公司 | Tetrazole type URAT1 inhibitors, preparing method, and uses of the inhibitors in treatment of hyperuricemia and gout |
-
2018
- 2018-04-28 CN CN201810396805.0A patent/CN108524518A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106032377A (en) * | 2015-03-12 | 2016-10-19 | 天津药物研究院有限公司 | Tetrazole type URAT1 inhibitors, preparing method, and uses of the inhibitors in treatment of hyperuricemia and gout |
Non-Patent Citations (1)
| Title |
|---|
| MING BIAN等: "Synthesis and anticonvulsant activity evaluation of 6-substituted-[1,2,4]triazolo[3,4-a](tetrazolo[5,1-a]) phthalazine derivatives", 《JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115232086A (en) * | 2022-07-19 | 2022-10-25 | 扬州市普林斯医药科技有限公司 | Preparation method of 4-benzyl-2 (3H) -oxazolone |
| CN115232086B (en) * | 2022-07-19 | 2024-05-03 | 扬州市普林斯医药科技有限公司 | Preparation method of 4-benzyl-2 (3H) -oxazolone |
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