CN108771679A - Purposes of the Cyclic dipeptides in preparing analgesic - Google Patents
Purposes of the Cyclic dipeptides in preparing analgesic Download PDFInfo
- Publication number
- CN108771679A CN108771679A CN201810232636.7A CN201810232636A CN108771679A CN 108771679 A CN108771679 A CN 108771679A CN 201810232636 A CN201810232636 A CN 201810232636A CN 108771679 A CN108771679 A CN 108771679A
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- China
- Prior art keywords
- cyclic dipeptides
- purposes
- preparation
- junket
- analgesic
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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
- A61K31/33—Heterocyclic compounds
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The purposes that the present invention provides Cyclic dipeptides in preparing analgesic, Cyclic dipeptides include L--L- junket Cyclic dipeptides, any one in D--L- junket Cyclic dipeptides or in its pharmaceutically acceptable derivates and its esters, it can extract from pangolin or manually be prepared, and be applied by different dosage forms.The Cyclic dipeptides of the present invention have exploitation at the potentiality of new type analgesic object, great scientific research and economic value.
Description
Technical field
The present invention relates to pharmaceutical field, be related to Cyclic dipeptides analgesic field new application, and in particular to Cyclic dipeptides exist
Prepare the purposes in analgesic.
Background technology
Cyclic dipeptides are shown anti-inflammatory, antitumor, anti-as a kind of active material at present by more and more concerns
A variety of significant bioactivity such as solidifying, neuroprotection, immunological regulation.Nowadays, anti-L--L- junket Cyclic dipeptides have been had not seen, D--
The report of L- junket Cyclic dipeptides analgesic activities.
Invention content
Technical problems to be solved：The object of the present invention is to provide a new class of Cyclic dipeptides with medical value and or its
Pharmaceutically acceptable derivates and its esters can be used for preparing new type analgesic object.
Technical solution：Purposes of the Cyclic dipeptides in preparing analgesic.
Further, the Cyclic dipeptides are L--L- junket Cyclic dipeptides, and in D--L- junket Cyclic dipeptides or it can pharmaceutically connect
Any one in the derivative and its esters received.
Further, the drug includes solid pharmaceutical preparation, semisolid preparation and liquid preparation, and wherein solid pharmaceutical preparation includes being
Tablet, capsule, granule, pill, sustained release preparation, controlled release preparation or patch, semisolid preparation include ointment, gel or bolt
Agent, liquid preparation include solution, injection, spray.
Further, using the Cyclic dipeptides as active constituent, in addition pharmaceutically acceptable auxiliary material or complementary ingredient system
It is standby to be used at drug.
Further, the Cyclic dipeptides are obtained or by being extracted from pangolin by artificial synthesized preparation.
Advantageous effect：The Cyclic dipeptides of the present invention can be used as effective ingredient, further prepare analgesic, for clinic
Treat pain caused by all kinds of reasons.
Specific implementation mode
With reference to specific embodiment, the present invention is described in detail.Following embodiment will be helpful to the technology of this field
Personnel further understand the present invention, but the invention is not limited in any way.It should be pointed out that the ordinary skill of this field
For personnel, without departing from the inventive concept of the premise, various modifications and improvements can be made.These belong to the present invention
Protection domain.
1, experimental animal：
Healthy Kunming mouse, SPF grades, weight 180-220g.That day alternates with night is only in 12h-12h for experimental animal feeding
In vertical environment, room temperature maintains 24 ± 2 DEG C, free water and ingests, and is tested after adapting to environment 1 week.To the institute of animal
There is processing to follow the requirement of Ethics Committee of International Association for Pain Research.
2, test drug and reagent：
Physiological saline, aspirin, acetum are commercially available；L--L- junket Cyclic dipeptides, D--L- junket Cyclic dipeptides self-controls,
Preparation method is：
（1）Pangolin medicinal material sand is fried and is processed as stir-baked SQUAMA MANITIS or vinegar naze；
（2）Stir-baked SQUAMA MANITIS or vinegar naze are beaten into powder, is sieved, extracting solution and the dregs of a decoction is then obtained by degreasing after the first solvent extraction,
The dregs of a decoction after first solvent extraction are obtained into extracting solution by the second solvent extraction again, extracting solution twice is merged, decompression is dense
Contracting obtains medicinal extract；
（3）Silica gel upper prop is mixed into the dissolving of medicinal extract methanol, stationary phase is 200-300 mesh silica gel, is dichloromethane with mobile phase, third
The colour developing monitoring of TLC iodine, combined dichloromethane, the fraction of acetone and ethyl alcohol is used in combination in ketone and ethanol elution；
（4）By step（3）Obtained fraction is purified with reversed-phase high performance liquid chromatography, and with second eyeball-water flowing phase, eluent decompression is dense
Contracting remove second eyeball and, it is dry, obtain the L- silks-L- junket Cyclic dipeptides and D--L- junket Cyclic dipeptides of 96% or more purity.
3, experimental method：
96 Kunming mouses are taken to be divided into L--L- junket Cyclic dipeptides, D--L- junket Cyclic dipeptides 2 administration groups, negative control groups
And positive controls, every group 12, half male and half female, suspension solution gastric infusion.L--L- junket Cyclic dipeptides, D--L- junket rings two
Peptide（10mg/kg）, positive to organize gavage aspirin (100mg/kg) administration, negative control group is given same dosage physiological saline and is filled
Stomach, continuous 5 d.1h after mouse last gavage, by medicine volume:The weight of animals is 0.1mL:2Og gives mouse peritoneal injection
0.6% acetum.
4, the computational methods of analgesia inhibiting rate：
Licking foot reaction two kinds of Cyclic dipeptides of observation with hot plate leads to thermostimulation the analgesic activity of mice pain, waits for that hot-plate instrument temperature is steady
When being scheduled on 55 DEG C, mouse is put into slot, right metapedes is licked as pain reaction index measured in advance pain threshold using mouse.It observes small
Mouse licks the sufficient response latency（That is the threshold of pain）And sufficient number is licked in 1min；
Ease pain inhibiting rate=(control group writhing number-administration group writhing number)/control group writhing number × 100%.
5, analgesic experiment data：It can be seen that L--L- junket Cyclic dipeptides and D--L- junket Cyclic dipeptides from the following table 1 and table 2
Have the effect of that apparent inhibition of pain, Cyclic dipeptides of the invention can be used as effective ingredient, further prepare analgesic, uses
The pain caused by all kinds of reasons of clinical treatment.
1 each group mouse writhing method test result (n=12) of table
* compared with negative control group, P < 0.01.
2 each group hot plate method in mice test result (n=12) of table
| Group | Lick the sufficient response latency（S） | Lick sufficient number（It is secondary） |
| Negative control group | 17.52+5.81 | 16.31+2.77 |
| L--L- junket Cyclic dipeptides | 29.21+3.26* | 11.23+1.99* |
| D--L- junket Cyclic dipeptides | 41.11+2.55* | 8.72+2.06* |
| Aspirin | 33.53+4.47* | 9.53+1.26* |
* compared with negative control group, P < 0.01.
Claims (5)
1. purposes of the Cyclic dipeptides in preparing analgesic.
2. purposes of the Cyclic dipeptides according to claim 1 in preparing analgesic, it is characterised in that：The Cyclic dipeptides are
L--L- junket Cyclic dipeptides, it is any one in D--L- junket Cyclic dipeptides or in its pharmaceutically acceptable derivates and its esters
Kind.
3. purposes of the Cyclic dipeptides according to claim 1 in preparing analgesic, it is characterised in that：The drug includes
Solid pharmaceutical preparation, semisolid preparation and liquid preparation, wherein solid pharmaceutical preparation include for tablet, capsule, granule, pill, sustained release
Preparation, controlled release preparation or patch, semisolid preparation include ointment, gel or suppository, and liquid preparation includes solution, injection
Agent, spray.
4. purposes of the Cyclic dipeptides according to claim 1 in preparing analgesic, it is characterised in that：With the Cyclic dipeptides
For active constituent, used in addition pharmaceutically acceptable auxiliary material or complementary ingredient are prepared into drug.
5. purposes of the Cyclic dipeptides according to claim 1 in preparing analgesic, it is characterised in that：The Cyclic dipeptides are logical
It crosses to extract from pangolin and obtain or by artificial synthesized preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810232636.7A CN108771679A (en) | 2018-03-21 | 2018-03-21 | Purposes of the Cyclic dipeptides in preparing analgesic |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810232636.7A CN108771679A (en) | 2018-03-21 | 2018-03-21 | Purposes of the Cyclic dipeptides in preparing analgesic |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108771679A true CN108771679A (en) | 2018-11-09 |
Family
ID=64033634
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810232636.7A Pending CN108771679A (en) | 2018-03-21 | 2018-03-21 | Purposes of the Cyclic dipeptides in preparing analgesic |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108771679A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996016982A2 (en) * | 1994-11-30 | 1996-06-06 | The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Ultraselective opioidmimetic peptides and pharmacological and therapeutic uses thereof |
| CN105288585A (en) * | 2014-06-18 | 2016-02-03 | 陈光健 | Application of cyclic dipeptide in preparation of drugs for treating skin injury |
-
2018
- 2018-03-21 CN CN201810232636.7A patent/CN108771679A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996016982A2 (en) * | 1994-11-30 | 1996-06-06 | The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Ultraselective opioidmimetic peptides and pharmacological and therapeutic uses thereof |
| CN105288585A (en) * | 2014-06-18 | 2016-02-03 | 陈光健 | Application of cyclic dipeptide in preparation of drugs for treating skin injury |
Non-Patent Citations (2)
| Title |
|---|
| 吴珊: "《穿山甲鳞甲乙醇提取物镇痛抗炎作用及其机制的实验研究》", 《广西医科大学硕士论文》 * |
| 马雪梅: "《穿山甲化学成分的研究》", 《药学学报》 * |
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| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20181109 |
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| RJ01 | Rejection of invention patent application after publication |