CN107308170A - Application and anti-inflammatory pharmaceutical compositions of the drug combination in anti-inflammatory drug is prepared - Google Patents
Application and anti-inflammatory pharmaceutical compositions of the drug combination in anti-inflammatory drug is prepared Download PDFInfo
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- CN107308170A CN107308170A CN201710555094.2A CN201710555094A CN107308170A CN 107308170 A CN107308170 A CN 107308170A CN 201710555094 A CN201710555094 A CN 201710555094A CN 107308170 A CN107308170 A CN 107308170A
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- bufalin
- resibufogenin
- telecinobufagin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
- A61K31/585—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin containing lactone rings, e.g. oxandrolone, bufalin
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Abstract
The present invention relates to drug field, application and anti-inflammatory pharmaceutical compositions of a kind of drug combination in anti-inflammatory drug is prepared are specifically disclosed.Described anti-inflammatory pharmaceutical compositions include Bufalin, resibufogenin and telecinobufagin；The weight ratio of described Bufalin, resibufogenin and telecinobufagin is 1 ~ 5:1~4:1~2.Collaboration antiinflammatory action can be played after Bufalin, resibufogenin and telecinobufagin mixing in the composition, especially by Bufalin, resibufogenin and telecinobufagin by weight 1.5 ~ 3:1~2:It cooperates with antiphlogistic effects to become apparent from after 1 mixing；In addition, can occur mutual attenuation after Bufalin, resibufogenin and telecinobufagin three are mixed, injury of the medicine to human body can be reduced, is conducive to drug safety.
Description
Technical field
The present invention relates to drug field, and in particular to application and anti-inflammatory drug of the drug combination in anti-inflammatory drug is prepared
Composition.
Background technology
Inflammation, is exactly " inflammation " usually described in people, is a kind of defense reaction of the body for stimulation, show as it is red,
Swollen, heat, pain and dysfunction.Anti-inflammatory agent is the medicine for treating the reaction-inflammation occurred after tissue sustains damage.Mesh
Preceding common anti-inflammatory agent has two major classes：One class is that the glucocorticoid hydrogenation secreted by steroidal anti-inflammatory medicine, i.e. adrenal cortex can
Loose and its artificial synthesized derivative.Another kind of is NSAIDs (NSAIDs, non-steroid-anti-
Inflammatory drugs), i.e. antipyretic-antalgic anti-inflammatory agent signified in medical practice such as aspirin, phenylbutazone, plug carrys out former times
Cloth etc..
The dried venom of toads is the secretion of toad ear rear gland and epidermal gland, white milky liquid or pale yellow syrup, poisonous.The dried venom of toads
Slurries are extracted, are dried, are painted, can be used as medicine after sealing preserve.With detoxifying, ease pain, have one's ideas straightened out, a variety of functions such as antitumor and by
Extensive use.It is existing studies have found that, substantial amounts of arenobufagin class, steroid and alkaloids chemical composition are contained in the dried venom of toads,
Also have been reported that a part of bufanolide has antiinflammatory action, or but some compound antiinflammatory actions are too weak, or
Some have the toxicity of compound of excellent antiinflammatory action too strong larger to injury of human, so causing bufanolide very
Hardly possible is used to use as anti-inflammatory drug.Therefore, using bufanolide as starting point, a kind of specific chemical components of exploitation,
Efficiently, the anti-inflammatory drug of low toxicity has wide market prospects.
The content of the invention
The technical problems to be solved by the invention are to provide a kind of anti-inflammatory pharmaceutical compositions.
Above-mentioned technical problem to be solved by this invention, is achieved by the following technical programs：
Present invention firstly provides Bufalin, resibufogenin and telecinobufagin combination answering in anti-inflammatory drug is prepared
With.
Preferably, the weight ratio of described Bufalin, resibufogenin and telecinobufagin is 1~5:1~4:1~2.
It is further preferred that the weight ratio of described Bufalin, resibufogenin and telecinobufagin is 1~4:1~
3:1。
It is further preferred that the weight ratio of described Bufalin, resibufogenin and telecinobufagin is 1.5~3:
1~2:1.
The present invention shows by lot of experiments, by energy after the combination of Bufalin, resibufogenin and telecinobufagin
Generation obviously cooperates with antiinflammatory action, and can be mutually attenuated after three's combination, and experiment shows that it can be effectively reduced pair
The toxicity of cell.Therefore, it can make after Bufalin, resibufogenin and telecinobufagin three being combined as anti-inflammatory drug
With.
The present invention also provides a kind of anti-inflammatory pharmaceutical compositions, and it includes Bufalin, resibufogenin and telecinobufagin；
The weight ratio of described Bufalin, resibufogenin and telecinobufagin is 1~5:1~4:1~2.
Preferably, the weight ratio of described Bufalin, resibufogenin and telecinobufagin is 1~4:1~3:1.
It is further preferred that the weight ratio of described Bufalin, resibufogenin and telecinobufagin is 1.5~3:1
~2:1.
Preferably, described anti-inflammatory pharmaceutical compositions also include pharmaceutically acceptable carrier.
Preferably, the formulation of described anti-inflammatory pharmaceutical compositions is liquid injection agent, powder-injection, tablet, capsule, flexible glue
Capsule, powder, pill, oral liquid, paste, granule or dressing.
Beneficial effect：The invention provides a kind of anti-inflammatory pharmaceutical compositions completely newly constituted, Bufalin, ester toad in composition
Can be played after the mixing of malicious aglucon and telecinobufagin and cooperate with antiinflammatory action, especially by Bufalin, resibufogenin and far
Cinobufagin is by weight 1.5~3:1~2:It cooperates with antiphlogistic effects to become apparent from after 1 mixing；In addition, by Bufalin, ester toadpoison
Mutual attenuation can occur after aglucon and telecinobufagin three mixing, embodiment experiment shows, energy after three's mixing
Substantially reduce the toxicity to cell.
Embodiment
The present invention is explained further below in conjunction with specific embodiment, but embodiment does not do any type of limit to the present invention
It is fixed.
The Bufalin of embodiment 1, resibufogenin and telecinobufagin drug combination anti-inflammation test
Male Kunming strain mice 160 is taken, body weight is 20 ± 2g, be randomly divided into blank control group, positive drug control group (sun
Property medicine be aspirin, dosage is 150mg/kg), experimental group 1~14 (dosage is 10mg/kg), by positive control
Medicine and experimental group medicine to be measured add water wiring solution-forming, carry out gastric infusion, and blank control group gives physiological saline, successive administration
5 days, 1 time a day, 1h smeared the μ L of dimethylbenzene 50 in mouse right ear and causes inflammation after last dose, and left ear is not processed.Put to death after 1h small
Mouse, two ears are cut along auricle baseline, break into round auricle at same position with 0.7cm card punch, electronic balance is weighed immediately, with
The difference of left and right auricle weight is used as swelling.
The medication composition of each experimental group is as follows：
Bufalin is used alone in experimental group 1；
Resibufogenin is used alone in experimental group 2；
Telecinobufagin is used alone in experimental group 3；
Experimental group 4 is 2 using weight ratio:1.5 Bufalin and resibufogenin；
Experimental group 5 is 1.5 using weight ratio:1 resibufogenin and telecinobufagin；
Experimental group 6 is 2 using weight ratio:1 Bufalin and telecinobufagin；
Experimental group 7 is 2 using weight ratio:1.5:1 Bufalin, resibufogenin and telecinobufagin；
Experimental group 8 is 2 using weight ratio:2:1 Bufalin, resibufogenin and telecinobufagin；
Experimental group 9 is 2 using weight ratio:1:1 Bufalin, resibufogenin and telecinobufagin；
Experimental group 10 is 3 using weight ratio:1.5:1 Bufalin, resibufogenin and telecinobufagin；
Experimental group 11 is 3 using weight ratio:1:1 Bufalin, resibufogenin and telecinobufagin；
Experimental group 12 is 3 using weight ratio:2:1 Bufalin, resibufogenin and telecinobufagin；
Experimental group 13 is 1.5 using weight ratio:1:1 Bufalin, resibufogenin and telecinobufagin；
Experimental group 14 is 1.5 using weight ratio:2:1 Bufalin, resibufogenin and telecinobufagin；
Experimental group 15 is 4 using weight ratio:2:1 Bufalin, resibufogenin and telecinobufagin；
Experimental group 16 is 2 using weight ratio:3:1 Bufalin, resibufogenin and telecinobufagin；
Experimental group 17 is 5 using weight ratio:3:1 Bufalin, resibufogenin and telecinobufagin；
Experimental group 18 is 3 using weight ratio:4:1 Bufalin, resibufogenin and telecinobufagin；
Experimental group 19 is 1 using weight ratio:1:2 Bufalin, resibufogenin and telecinobufagin；
Experimental group 20 is 1 using weight ratio:2:2 Bufalin, resibufogenin and telecinobufagin.
The anti-inflammation test result of the Bufalin of table 1., resibufogenin and telecinobufagin drug combination
Note：Represent that ## represents that P ＜ 0.01, # represent P ＜ 0.05 compared with blank control group
As can be seen from Table 1, when Bufalin, resibufogenin or telecinobufagin is used alone, two can be suppressed
Mouse right ear swelling caused by toluene, illustrates that it has certain antiinflammatory action, but can from the swelling of experimental group 1~3
Go out, in this experiment, its swelling is more than positive control drug aspirin, this illustrates the anti-inflammatory effect of aspirin in this experiment
Fruit is better than Bufalin, resibufogenin or telecinobufagin.
It is can be seen that from the experimental data of embodiment 4~6 when Bufalin, resibufogenin and telecinobufagin are mixed two-by-two
During conjunction, less, this explanation Bufalin, resibufogenin and telecinobufagin are mixed two-by-two for its swelling and exclusive use phase difference
When, for its antiinflammatory action can not be lifted.
Embodiment 7~20 is the mixing of Bufalin, resibufogenin and telecinobufagin three, from embodiment 7~20
Swelling degrees of data can be seen that the swelling that its swelling degrees of data is respectively less than the 8.56mg of aspirin, far smaller than Bufalin,
Resibufogenin and telecinobufagin are used alone or any mixing of the two, this explanation Bufalin, resibufogenin and remote China
Collaboration antiinflammatory action can be produced between the mixing latter three of bufagin three so that antiphlogistic effects are significantly enhanced.Especially
It is embodiment 7~14, its swelling is minimum, respectively less than 3.27mg, the 8.56mg of much small aspirin swelling, and this says
The bright weight ratio when Bufalin, resibufogenin and telecinobufagin is 1.5~3:1~2:During 1 scope, it cooperates with anti-inflammatory effect
Fruit preferably, is much better than positive control drug aspirin in this experiment.
The Bufalin of embodiment 2, resibufogenin and telecinobufagin combination cytotoxicity test
By Hep-2 cell culture in 96 well culture plates, after cell monolayer length is good, what addition maintaining liquid had diluted is
The μ L of row concentration samples solution 100, in 5%CO2, cultivate 3 days in 37 DEG C of incubators；Then 10 μ lMTT solution, MTT solution are added
Concentration be 5mg/mL, configured with cushioning liquid, continue cultivate 4 hours；Sample solution is suctioned out, dimethyl sulfoxide is added, at room temperature,
96 orifice plates are placed in micro- emptying aperture plate oscillator and vibrated 10 minutes；The OD values in each hole are determined with ELIASA, measurement wavelength is
570nm, reference wavelength is 630nm, calculates median lethal toxic concentration (CC of the sample to cell50).Every group sets 4 balance pipes,
Every group of experiment is repeated 3 times.Result of calculation, draws curve, obtains half toxic concentration (CC50)。
Testing sample is respectively：Resibufogenin；Bufalin；Telecinobufagin；Bufalin：Resibufogenin (2:1.5)；
Resibufogenin：Telecinobufagin (1.5:1)；Bufalin：Telecinobufagin (2:1)；Bufalin：Resibufogenin：Remote China's toad
Bufonid toad essence (2:1.5:1)；Bufalin：Resibufogenin：Telecinobufagin (2:1:1)；Bufalin：Resibufogenin：Remote China toad
Essence (3:2:1)；Bufalin：Resibufogenin：Telecinobufagin (1.5:2:1)；Bufalin：Resibufogenin：Telecinobufagin
(4:2:1)；Bufalin：Resibufogenin：Telecinobufagin (5:3:1)；Bufalin：Resibufogenin：Telecinobufagin (1:2:
2)；Aforementioned proportion is weight ratio.
The cytotoxicity test test result of table 2.
As can be seen that Bufalin, resibufogenin and telecinobufagin or the group of the two is used alone from the data of table 2
Close, its CC to cell50Value is far smaller than the combination of Bufalin, resibufogenin and telecinobufagin three, this explanation toad
Can occur mutual attenuation after the combination of malicious spirit, resibufogenin and telecinobufagin three so that after three's combination
Cytotoxicity is greatly reduced；This also illustrates after the combination of Bufalin, resibufogenin and telecinobufagin three using can be with
Injury of the medicine to human body is reduced, is conducive to drug safety.
The anti-inflammatory pharmaceutical compositions of embodiment 3
By Bufalin, resibufogenin and telecinobufagin by weight 2:1.5:1 mixing is as active ingredient, then
Powder-injection is made by the conventional method of pharmaceutical field.
The anti-inflammatory pharmaceutical compositions of embodiment 4
By Bufalin, resibufogenin and telecinobufagin by weight 3:2:Then 1 mixing presses as active ingredient
Powder-injection is made in the conventional method of pharmaceutical field.
The anti-inflammatory pharmaceutical compositions of embodiment 5
By Bufalin, resibufogenin and telecinobufagin by weight 3:2:Then 1 mixing presses as active ingredient
Liquid injection agent is made in the conventional method of pharmaceutical field.
The anti-inflammatory pharmaceutical compositions of embodiment 6
By Bufalin, resibufogenin and telecinobufagin by weight 3:1:Then 1 mixing presses as active ingredient
Tablet is made in the conventional method of pharmaceutical field.
The anti-inflammatory pharmaceutical compositions of embodiment 7
By Bufalin, resibufogenin and telecinobufagin by weight 4:2:Then 1 mixing presses as active ingredient
Capsule is made in the conventional method of pharmaceutical field.
The anti-inflammatory pharmaceutical compositions of embodiment 8
By Bufalin, resibufogenin and telecinobufagin by weight 4:3:Then 1 mixing presses as active ingredient
Powder is made in the conventional method of pharmaceutical field.
The anti-inflammatory pharmaceutical compositions of embodiment 9
By Bufalin, resibufogenin and telecinobufagin by weight 2:3:Then 1 mixing presses as active ingredient
Pill is made in the conventional method of pharmaceutical field.
The anti-inflammatory pharmaceutical compositions of embodiment 10
By Bufalin, resibufogenin and telecinobufagin by weight 5:3:Then 1 mixing presses as active ingredient
Oral liquid is made in the conventional method of pharmaceutical field.
The anti-inflammatory pharmaceutical compositions of embodiment 11
By Bufalin, resibufogenin and telecinobufagin by weight 1:1:Then 2 mixing press as active ingredient
Paste is made in the conventional method of pharmaceutical field.
The anti-inflammatory pharmaceutical compositions of embodiment 12
By Bufalin, resibufogenin and telecinobufagin by weight 1:2:Then 2 mixing press as active ingredient
Granule is made in the conventional method of pharmaceutical field.
The anti-inflammatory pharmaceutical compositions of embodiment 13
By Bufalin, resibufogenin and telecinobufagin by weight 5:1:Then 2 mixing press as active ingredient
Dressing is made in the conventional method of pharmaceutical field.
Claims (9)
1. Bufalin, resibufogenin and telecinobufagin are combined the application in anti-inflammatory drug is prepared.
2. application according to claim 1, it is characterised in that described Bufalin, resibufogenin and remote magnificent toad
The weight ratio of essence is 1 ~ 5:1~4:1~2.
3. application according to claim 2, it is characterised in that described Bufalin, resibufogenin and remote magnificent toad
The weight ratio of essence is 1 ~ 4:1~3:1.
4. application according to claim 3, it is characterised in that described Bufalin, resibufogenin and remote magnificent toad
The weight ratio of essence is 1.5 ~ 3:1~2:1.
5. a kind of anti-inflammatory pharmaceutical compositions, it is characterised in that include Bufalin, resibufogenin and telecinobufagin；It is described
Bufalin, the weight ratio of resibufogenin and telecinobufagin be 1 ~ 5:1~4:1~2.
6. anti-inflammatory pharmaceutical compositions according to claim 5, it is characterised in that described Bufalin, resibufogenin with
And the weight ratio of telecinobufagin is 1 ~ 4:1~3:1.
7. anti-inflammatory pharmaceutical compositions according to claim 6, it is characterised in that described Bufalin, resibufogenin with
And the weight ratio of telecinobufagin is 1.5 ~ 3:1~2:1.
8. anti-inflammatory pharmaceutical compositions according to claim 5, it is characterised in that described anti-inflammatory pharmaceutical compositions are also included
Pharmaceutically acceptable carrier.
9. anti-inflammatory pharmaceutical compositions according to claim 5, it is characterised in that the formulation of described anti-inflammatory pharmaceutical compositions
For liquid injection agent, powder-injection, tablet, capsule, soft capsule, powder, pill, oral liquid, paste, granule or dressing.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710555094.2A CN107308170A (en) | 2017-07-10 | 2017-07-10 | Application and anti-inflammatory pharmaceutical compositions of the drug combination in anti-inflammatory drug is prepared |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710555094.2A CN107308170A (en) | 2017-07-10 | 2017-07-10 | Application and anti-inflammatory pharmaceutical compositions of the drug combination in anti-inflammatory drug is prepared |
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| CN107308170A true CN107308170A (en) | 2017-11-03 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109718229A (en) * | 2019-02-15 | 2019-05-07 | 烟台汉麻生物技术有限公司 | A kind of anti-inflammatory pharmaceutical compositions and its application |
| CN112679579A (en) * | 2020-12-29 | 2021-04-20 | 潍坊医学院 | Analgesic peptide CI5 separated from cinobufotalin injection and application thereof |
| CN114404425A (en) * | 2022-01-27 | 2022-04-29 | 南京中医药大学 | Inhibitor of phosphodiesterase and application thereof |
-
2017
- 2017-07-10 CN CN201710555094.2A patent/CN107308170A/en active Pending
Non-Patent Citations (2)
| Title |
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| 刘冬等: "蟾酥提取物中2 种蟾蜍甾烯类成分兔体内药代动力学研究", 《中国实验方剂学杂志》 * |
| 曹徐涛等: "蟾皮中蟾毒配基类成分的分离与鉴定", 《沈阳药科大学学报》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109718229A (en) * | 2019-02-15 | 2019-05-07 | 烟台汉麻生物技术有限公司 | A kind of anti-inflammatory pharmaceutical compositions and its application |
| CN109718229B (en) * | 2019-02-15 | 2021-05-28 | 烟台汉麻生物技术有限公司 | Anti-inflammatory pharmaceutical composition and application thereof |
| CN112679579A (en) * | 2020-12-29 | 2021-04-20 | 潍坊医学院 | Analgesic peptide CI5 separated from cinobufotalin injection and application thereof |
| CN114404425A (en) * | 2022-01-27 | 2022-04-29 | 南京中医药大学 | Inhibitor of phosphodiesterase and application thereof |
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