CN115089583A - Application of compound in preparation of medicine for preventing or treating intervertebral disc degeneration - Google Patents
Application of compound in preparation of medicine for preventing or treating intervertebral disc degeneration Download PDFInfo
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- CN115089583A CN115089583A CN202210848510.9A CN202210848510A CN115089583A CN 115089583 A CN115089583 A CN 115089583A CN 202210848510 A CN202210848510 A CN 202210848510A CN 115089583 A CN115089583 A CN 115089583A
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- intervertebral disc
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- 206010061246 Intervertebral disc degeneration Diseases 0.000 title claims abstract description 45
- 208000018180 degenerative disc disease Diseases 0.000 title claims abstract description 38
- 208000021600 intervertebral disc degenerative disease Diseases 0.000 title claims abstract description 38
- 150000001875 compounds Chemical class 0.000 title claims abstract description 34
- 239000003814 drug Substances 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims abstract description 5
- 239000004480 active ingredient Substances 0.000 claims abstract description 4
- 239000007924 injection Substances 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 238000013268 sustained release Methods 0.000 claims description 2
- 239000012730 sustained-release form Substances 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims 3
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 abstract description 7
- 238000002474 experimental method Methods 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 3
- 241000700159 Rattus Species 0.000 description 16
- 208000008930 Low Back Pain Diseases 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 208000008035 Back Pain Diseases 0.000 description 3
- 230000007850 degeneration Effects 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- RZSYLLSAWYUBPE-UHFFFAOYSA-L Fast green FCF Chemical compound [Na+].[Na+].C=1C=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C(=CC(O)=CC=2)S([O-])(=O)=O)C=CC=1N(CC)CC1=CC=CC(S([O-])(=O)=O)=C1 RZSYLLSAWYUBPE-UHFFFAOYSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 210000002744 extracellular matrix Anatomy 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 238000002595 magnetic resonance imaging Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000032984 Intraoperative Complications Diseases 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- HEKAIDKUDLCBRU-UHFFFAOYSA-N N-[4-[2-ethyl-4-(3-methylphenyl)-5-thiazolyl]-2-pyridinyl]benzamide Chemical compound S1C(CC)=NC(C=2C=C(C)C=CC=2)=C1C(C=1)=CC=NC=1NC(=O)C1=CC=CC=C1 HEKAIDKUDLCBRU-UHFFFAOYSA-N 0.000 description 1
- 208000035965 Postoperative Complications Diseases 0.000 description 1
- 206010057765 Procedural complication Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000001195 anabolic effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000000249 desinfective effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000013505 freshwater Substances 0.000 description 1
- 230000005861 gene abnormality Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 235000018343 nutrient deficiency Nutrition 0.000 description 1
- 238000002559 palpation Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- OARRHUQTFTUEOS-UHFFFAOYSA-N safranin Chemical compound [Cl-].C=12C=C(N)C(C)=CC2=NC2=CC(C)=C(N)C=C2[N+]=1C1=CC=CC=C1 OARRHUQTFTUEOS-UHFFFAOYSA-N 0.000 description 1
- 208000013363 skeletal muscle disease Diseases 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
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Classifications
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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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Physical Education & Sports Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to the technical field of medicines, and particularly discloses application of a compound in preparation of a medicine for preventing or treating intervertebral disc degeneration. The inventor finds out in experiments that: the intervertebral disc height and signals of the rat with the intervertebral disc degeneration model are reduced compared with those of a normal control group; after the compound with the structure shown in the formula I is locally injected in the treatment group, the height and the signal of the intervertebral disc are higher than those of the model group; the experimental result shows that the compound with the structure shown in the formula I has the treatment effect on the intervertebral disc degeneration; therefore, the compound with the structure shown in the formula I as an active ingredient has important application value in preparing the medicines for preventing or treating the intervertebral disc degeneration.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to application of a compound in preparing a medicine for preventing or treating intervertebral disc degeneration.
Background
Low back pain (Low back pain) is a skeletal muscle disease that is widely present in clinical settings. It is reported that up to 80% of people are affected by low back pain in their lives, causing a great economic and medical burden. Intervertebral Disc Degeneration (IDD) is the most common cause of lower back pain, accounting for about 40%. However, no therapeutic drug for intervertebral disc degeneration exists in the clinic at present.
Intervertebral disc degeneration is a multifactorial process, such as abnormal stress, local nutritional deficiency, congenital gene abnormality and the like, and inflammation is one of the important pathogenesis of intervertebral disc degeneration, wherein the inflammatory factor-mediated anabolic disorder of nucleus pulposus extracellular matrix is a very critical ring in the intervertebral disc degeneration process. Therefore, in recent years, research on the degradation and loss of the extracellular matrix of nucleus pulposus cells mediated by inflammatory factors becomes an important way for treating the degeneration of the intervertebral disc, so as to fundamentally solve the problem of the degeneration of the intervertebral disc.
At present, the clinically used treatment medicines are mostly used for specific symptoms, the types of related medicines for protecting and improving the degenerative intervertebral disc are few, and the selection of patients is small. Meanwhile, the existing drugs have limited curative effect and have certain side effect after long-term application, so the use is limited to a certain extent. The operation treatment mainly comprises lumbar vertebra fusion and intervertebral disc replacement, wherein the lumbar vertebra fusion is to remove an intervertebral disc and implant an internal fixation and an intervertebral fusion device afterwards, the wound is large, the problems of related intraoperative and postoperative complications and the like exist, and the mobility of a fixed section after the operation is lost; economically, the high consumption of implants and instruments places a load bearing burden on society and families. Therefore, the development of a medicament for preventing or treating intervertebral disc degeneration has important application value.
Disclosure of Invention
In order to solve at least one of the technical problems indicated in the prior art, the invention provides the application of a compound in preparing a medicament for preventing or treating intervertebral disc degeneration.
The technical problem to be solved by the invention is realized by the following technical scheme:
the application of a compound in preparing a medicament for preventing or treating intervertebral disc degeneration, wherein the compound has a structure shown in a formula I;
the compound with the structure shown in the formula I is a known compound, and the inventor surprisingly discovers in an experiment that the intervertebral disc height and the signal of an intervertebral disc degeneration model rat are reduced compared with those of a normal control group; after the compound with the structure shown in the formula I is locally injected in the treatment group, the height and the signal of the intervertebral disc are higher than those of the model group; experiments show that the compound with the structure shown in the formula I has a therapeutic effect on intervertebral disc degeneration.
The compound with the structure shown in the formula I has the function of preventing or treating intervertebral disc degeneration; therefore, it is regarded as
Preferably, the medicine takes a compound with a structure shown in a formula I as an active ingredient.
Preferably, the medicament further comprises pharmaceutically acceptable auxiliary materials.
Preferably, the dosage form of the medicament comprises: injection, oral liquid, capsule, tablet, granule, sustained release agent and drop pill.
Has the advantages that: the invention provides a brand new application of a compound with a structure shown in a formula I in preparing a medicament for preventing or treating intervertebral disc degeneration. The inventor finds out in experiments that: the intervertebral disc height and signals of the rat with the intervertebral disc degeneration model are reduced compared with those of a normal control group; after the compound with the structure shown in the formula I is locally injected in the treatment group, the height and the signal of the intervertebral disc are higher than those of the model group; the experimental result shows that the compound with the structure shown in the formula I has the therapeutic effect on intervertebral disc degeneration; therefore, the compound with the structure shown in the formula I as an active ingredient has important application value in preparing medicines for preventing or treating intervertebral disc degeneration.
Drawings
FIG. 1 shows MRI images of rat caudal vertebrae (wherein CTR is a control group, IDD is a simple disc degeneration group, and IDD + TAK is a disc degeneration + compound treatment group having a structure represented by formula I).
FIG. 2 shows the fast-green staining patterns of rat caudal vertebra HE and crimson O (wherein CTR is a control group, IDD is a single disc degeneration group, and IDD + TAK is disc degeneration + compound treatment group with structure shown in formula I).
Detailed Description
The present invention is further explained below with reference to specific examples, which are not intended to limit the present invention in any way.
EXAMPLE 1 Compounds of formula I have therapeutic effects on intervertebral disc degeneration
1) Rat caudal vertebra puncture model and rescue by using TAK-715
Male SD rats (animal laboratory of Zhongshan medical school of Zhongshan university) of 8 weeks old were collected at 26-28 deg.C and 50-65% humidity for 12 hours day and night. Animals were fed standard rodent chow and were given fresh water ad libitum. Prior to surgery, rats were anesthetized by intraperitoneal injection of sodium pentobarbital (5mg/100g body weight). And (3) disinfecting the tail part, judging whether a puncture segment (Co8/9) or a puncture needle (21G) penetrates into the center of the intervertebral disc and traverses the whole fiber ring (AF) layer by means of finger tip palpation, wherein the puncture depth is about 4mm, the puncture needle is left in the intervertebral disc for 1 minute, the puncture needle is pulled out, and the puncture part is disinfected, namely the intervertebral disc degeneration model is established.
Rats were grouped: group 1 (Control group, Control in fig. 1), group 2 (simple disc degeneration group, IDD in fig. 1), and group 3 (disc degeneration + compound treatment group of formula i, IDD + TAK in fig. 1).
Group 1 was normal male SD rats, and group 2 and group 3 were intervertebral disc degeneration model rats, respectively; each group had 6.
2) In vivo injection using a compound of formula I and a control
Group 3 rats were each injected intradiscally with 5. mu.l of a compound of the formula I (1. mu.M). Rats were given 8 weeks of post-treatment recovery.
3) Detecting the degeneration condition of the intervertebral disc of each group of rats
MRI scanning of the tail vertebrae of the rats was performed, all rats were sacrificed, the tails removed, and then the soft tissue was removed and the spine was fixed with 4% PFA. The disc tissues were sectioned for histological evaluation into 5 μm thick paraffin sections, which were stained with safranin O fast green and HE according to standard laboratory protocols, and the results are shown in figure 2.
The experimental result shows that the intervertebral disc height and the signal of the rat with the intervertebral disc degeneration model are reduced compared with those of a control group. After the compound with the structure shown in the formula I is locally injected in the treatment group, the height of the intervertebral disc and the signal are higher than those of the model group. This demonstrates that compounds of the structure shown in formula I have therapeutic effects on intervertebral disc degeneration.
Claims (4)
1. The application of a compound in preparing a medicament for preventing or treating intervertebral disc degeneration is characterized in that the compound has a structure shown in a formula I;
2. the use of a compound according to claim 1 for the preparation of a medicament for the prevention or treatment of intervertebral disc degeneration, wherein said medicament comprises as an active ingredient a compound of formula i.
3. The use of a compound according to claim 1 in the manufacture of a medicament for the prevention or treatment of intervertebral disc degeneration, wherein said medicament further comprises a pharmaceutically acceptable excipient.
4. Use of a compound according to claim 1 for the preparation of a medicament for the prevention or treatment of intervertebral disc degeneration, wherein the medicament is in a dosage form comprising: injection, oral liquid, capsule, tablet, granule, sustained release agent and dripping pill.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210848510.9A CN115089583A (en) | 2022-07-19 | 2022-07-19 | Application of compound in preparation of medicine for preventing or treating intervertebral disc degeneration |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210848510.9A CN115089583A (en) | 2022-07-19 | 2022-07-19 | Application of compound in preparation of medicine for preventing or treating intervertebral disc degeneration |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115089583A true CN115089583A (en) | 2022-09-23 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210848510.9A Pending CN115089583A (en) | 2022-07-19 | 2022-07-19 | Application of compound in preparation of medicine for preventing or treating intervertebral disc degeneration |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115089583A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090162376A1 (en) * | 2007-12-21 | 2009-06-25 | Brown Laura J | Trans-capsular administration of p38 map kinase inhibitors into orthopedic joints |
| WO2022016267A1 (en) * | 2020-07-21 | 2022-01-27 | Haglund Lisbet Agneta | Senotherapeutic drugs for age-related diseases and cancer |
-
2022
- 2022-07-19 CN CN202210848510.9A patent/CN115089583A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090162376A1 (en) * | 2007-12-21 | 2009-06-25 | Brown Laura J | Trans-capsular administration of p38 map kinase inhibitors into orthopedic joints |
| WO2022016267A1 (en) * | 2020-07-21 | 2022-01-27 | Haglund Lisbet Agneta | Senotherapeutic drugs for age-related diseases and cancer |
Non-Patent Citations (2)
| Title |
|---|
| REBECCA K. STUDER等: "p38 MAPK Inhibition in Nucleus Pulposus Cells： A Potential Target for Treating Intervertebral Disc Degeneration", SPINE, vol. 32, no. 25, pages 2827 - 2833 * |
| SEIJI MIWATASHI等: "Novel Inhibitor of p38 MAP Kinase as an Anti-TNF-αα Drug: Discovery of N-[4-[2-Ethyl-4-(3-methylphenyl)-1,3-thiazol-5-yl]-2-pyridyl]benzamide (TAK-715) as a Potent and Orally Active Anti-Rheumatoid Arthritis Agent", J. MED. CHEM., vol. 48, no. 19, pages 5966 - 5979, XP009156155, DOI: 10.1021/jm050165o * |
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Application publication date: 20220923 |