CN107158486A - Jamaicin FirebirdTM - Google Patents
Jamaicin FirebirdTM Download PDFInfo
- Publication number
- CN107158486A CN107158486A CN201710181676.9A CN201710181676A CN107158486A CN 107158486 A CN107158486 A CN 107158486A CN 201710181676 A CN201710181676 A CN 201710181676A CN 107158486 A CN107158486 A CN 107158486A
- Authority
- CN
- China
- Prior art keywords
- jamaicin
- firebirdtm
- skeleton
- effect
- release
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- WITLAWYGGVAFLU-UHFFFAOYSA-N 3-(6-methoxy-1,3-benzodioxol-5-yl)-8,8-dimethylpyrano[2,3-f]chromen-4-one Chemical compound C1=CC(C)(C)OC2=CC=C(C(C(C3=CC=4OCOC=4C=C3OC)=CO3)=O)C3=C21 WITLAWYGGVAFLU-UHFFFAOYSA-N 0.000 title claims abstract description 130
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- PJRSUKFWFKUDTH-JWDJOUOUSA-N (2s)-6-amino-2-[[2-[[(2s)-2-[[(2s,3s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-6-amino-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[(2-aminoacetyl)amino]-4-methylsulfanylbutanoyl]amino]propanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]propanoyl]amino]acetyl]amino]propanoyl Chemical compound CSCC[C@H](NC(=O)CN)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(N)=O PJRSUKFWFKUDTH-JWDJOUOUSA-N 0.000 claims 1
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- 230000000694 effects Effects 0.000 abstract description 20
- YBHILYKTIRIUTE-UHFFFAOYSA-N berberine Chemical compound C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 YBHILYKTIRIUTE-UHFFFAOYSA-N 0.000 abstract description 13
- 229940093265 berberine Drugs 0.000 abstract description 12
- QISXPYZVZJBNDM-UHFFFAOYSA-N berberine Natural products COc1ccc2C=C3N(Cc2c1OC)C=Cc4cc5OCOc5cc34 QISXPYZVZJBNDM-UHFFFAOYSA-N 0.000 abstract description 12
- 210000000329 smooth muscle myocyte Anatomy 0.000 abstract description 11
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- 241001465754 Metazoa Species 0.000 description 10
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- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 6
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 6
- 238000010586 diagram Methods 0.000 description 5
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- 229960002930 sirolimus Drugs 0.000 description 3
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 3
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- QVCMHGGNRFRMAD-UHFFFAOYSA-N monocrotaline Natural products C1OC(=O)C(C)(O)C(O)(C)C(C)C(=O)OC2CCN3C2C1=CC3 QVCMHGGNRFRMAD-UHFFFAOYSA-N 0.000 description 2
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- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 2
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
-
- 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/02—Inorganic materials
- A61L31/022—Metals or alloys
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/10—Macromolecular materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/148—Materials at least partially resorbable by the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/42—Anti-thrombotic agents, anticoagulants, anti-platelet agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
Abstract
Release-controlled film is coated with a kind of jamaicin FirebirdTM, including medical metal skeleton, skeleton, the metallic framework is loaded with jamaicin.The anti-norepinephrine of jamaicin that the present invention is provided stimulates the effect of arteria pulmonalis smooth muscle cells to protrude, and ventricular function can be effectively improved, while mean pulmonary arterial pressure can be significantly reduced；It is also equipped with preventing and treating the effect of in-stent restenosis and thrombus in stents；Jamaicin has the unique effect for preventing and treating myocardial infarction, additionally it is possible to effectively prevent and treat ischemic cardiomyopathy and its caused heart failure.The berberine FirebirdTM that the present invention is provided includes being coated with release-controlled film on medical metal skeleton, skeleton, and the metallic framework is loaded with jamaicin.Berberine FirebirdTM has the effect of smooth muscle cell proliferation of significantly inhibiting, and can significantly improve the myocardial ischemia caused by hemadostewnosis, and can suppress restenotic lesions and thrombus in stents develops.
Description
Technical field
The invention belongs to bracket for eluting medicament technical field, and in particular to jamaicin FirebirdTM.
Background technology
Bracket for eluting medicament (DES) is also referred to as drug releasing stent, by the polymer for being coated in metal support surface
Medicine is carried, after support inserts vessel inner lesion position, is controlledly released by type of elution in medicine autohemagglutination compound coating
Put to vascular wall tissue and play biological effect.Wherein, medicine slow release stent is for realizing medicine in vivo slow controllable
Release has great importance.Degradable medicine slow release stent material due to that will not be detained residue without two in vivo
Secondary operation, so as to reduce the pain of patient.It is various in the bracket for eluting medicament species of zoopery and pre-clinical trials, on
The DES in city only has observation on sirolimus-eluting stent and Paclitaxel-Eluting.CYPHER supports carry drug rapamycin, and dosage is
148μg/cm2, rapamycin deenergized period is 28 days.Rapamycin is natural macrolide antibiotics, is resisted with stronger
Cell is bred and immunosuppressive action, is mainly acted on the vascular smooth muscle mitotic G1 phases, is stopped cell mitogen
In phase resting stage G0.TAXUS supports are then to carry drug taxol, and dosage is 1.0 μ g/mm2, slow release.Taxol can be made
For the vascular smooth muscle cells mitosis G2-M phases, suppress vascular smooth muscle cell proliferation.Jamaicin is also known as berberine.It is a kind of
Common morphinane alkaloid, molecular formula C20H18NO4.It is present in many plants of the section ten of Berberidaceae etc. four category.
M.-E. Xia Waliai and G. Pei Ertan are obtained first from Xanthoxylonclava barks within 1826.Jamaicin is a kind of season
Ammonium alkaloid.Yellow needle-like crystals can be separated out from ether；85-86 DEG C of fusing point；Water is dissolved in, benzene, ether and chloroform is insoluble in.Its
Solubility of the salt in water is all smaller, and such as hydrochloride is 1:500, sulfate is 1:30.Jamaicin is to hemolytic hammer
Bacterium, staphylococcus aureus, gonococcus and Freund, Shigella shigae etc. have antibacterial action, and have enhancing white blood cell to gulp down
The effect of biting, also there is different degrees of inhibitory action to tubercle bacillus, plague bacillus, also has suppression effectiveness to the amoeba bacterium of rat.
Jamaicin has anti-curare to act in animals, and with peripheral decompression and refrigeration function.The hydrochloride of jamaicin (is commonly called as
Halomine) treatment gastroenteritis, bacillary dysentery etc. are widely used in, to pulmonary tuberculosis, scarlet fever, acute tonsillitis and exhale
Inhaling road infection also has certain curative effect.Jamaicin still has reduction blood fat and adjusts the effect of blood glucose.
The content of the invention
The technical problem of solution：The present invention provides a kind of jamaicin FirebirdTM, and the stent applications can effectively change in clinic
Kind right ventricular function, while mean pulmonary arterial pressure can be significantly reduced, the effect of preventing and treating in-stent restenosis and thrombus in stents,
Myocardial infarction can be prevented and treated simultaneously, ischemic cardiomyopathy and its caused heart failure can also be prevented and treated.
Technical scheme：Release-controlled film, the metal are coated with jamaicin FirebirdTM, including medical metal skeleton, skeleton
Skeleton or release-controlled film are loaded with jamaicin.
It is preferred that, metallic framework is cochrome, 80~100 μm of skeleton thickness.Load pharmaceutical quantities 70- on metallic framework
180μg/mm2。
Above-mentioned release-controlled film is degradable membrane, and degradable membrane is poly (glycolide-lactide) (PGLA) or PLA (PLA)；Degradable membrane
Implant 3 days and discharge total pharmaceutical quantities 25wt.%, the 50wt.% of total pharmaceutical quantities is discharged after 7 days, total pharmaceutical quantities are discharged after 28 days
85wt.%；It is degradable in the degradable membrane 60 days.
Beneficial outcomes：Containing the jamaicin that can be sustained on the FirebirdTM that the present invention is provided, first kidney is removed using jamaicin is anti-
Upper parathyrine stimulates the effect of arteria pulmonalis smooth muscle cells to protrude, and right ventricular function can be effectively improved, while can significantly reduce
Mean pulmonary arterial pressure；It is also equipped with preventing and treating the effect of in-stent restenosis and thrombus in stents；Jamaicin, which has, prevents and treats myocardial infarction
Unique effect, additionally it is possible to effectively prevent and treat ischemic cardiomyopathy and its caused heart failure.
Brief description of the drawings
Fig. 1 is the anti-norepinephrine schematic diagram of jamaicin；Arteria pulmonalis smooth muscle cells pass through norepinephrine (NE)
After stimulating 2 hours, jamaicin group (Ctl groups, jamaicin is acted on 4 hours) and control group are randomly divided into.Control group is respectively at packet
Different time points collect cell in (- 4 hours 30 minutes) afterwards, determine liver kinase B1 (LKB1) and g protein coupled receptor kinases 2
(Grk2) protein phosphorylation activity.GAPDH is internal reference albumen；
Fig. 2 is that jamaicin suppresses pulmonary artery reconstruct contrast experiment's mirror image figure；Pulmonary hypertension animal is randomly divided into normal right
According to group, jamaicin group and untreated blank group.Histochemical stain (HE) and blood vessel endothelium vWF dyeing, smooth muscle cell dye
Color (SMA).Result shows that the reconstruct of jamaicin group Pulmonary Vascular pathology is notable and mitigated at 14 weeks；
Fig. 3 is that jamaicin significantly raises right ventricle contraction displacement amplitude (TAPSE) block diagram；Jamaicin treatment group right ventricle
Function is significantly improved；
Fig. 4 is that jamaicin reduces mean pulmonary arterial pressure comparative experimental data block diagram；Jamaicin treatment group pulmonary artery is averaged
Pressure is significantly reduced, and every three data posts are one group in figure, and normal group, blank group and jamaicin group are followed successively by from left to right；
Fig. 5 is that jamaicin prevents and treats in-stent restenosis experiment contrast figure；It is coronal before 79 years old patient with angina pectoris of women, stenting
Angiography shows the serious lower limb in Left main artery end, and support immediate postoperative shows narrow basic disappearance；Have a surplus again within postoperative 4th month
Make up one's mind angina, coronarography shows narrow in descending anterior branch opening and the serious support of Circumflex branch near-end, and accumulative Left main artery end
End；Coronarography shows that in-stent restenosis disappears substantially after persistently being treated 6 months using jamaicin；
Fig. 6 is the experimental result picture that jamaicin prevents and treats ischemic cardiomyopathy；Fluorescent staining (left side) and electron microscope (right A-
C) display jamaicin treatment group cardiac muscle cell apoptosis significantly mitigates；
Fig. 7 is that jamaicin significantly improves heart failure result of study figure caused by ischemic cardiomyopathy；One ischemic cardiac
Patients with myopathy shows that ventricular function seriously declines in the 22nd day open in-heart operation under pulsating after myocardial infarction, continuous to use jamaicin 3
Left ventricular ejection fraction substantially increases after individual month, myocardium shrinkage function is improved.
Fig. 8 is the use state images of jamaicin FirebirdTM；
Fig. 9 is the sustained release rule schematic diagram of jamaicin FirebirdTM.
Figure 10 is berberine and GRK2 signal paths and smooth muscle cell interactively schematic diagram.It is up, with control group phase
Than (left side), go plus adrenaline (NE) stimulate artery smooth muscle cell migration showed increased (in), and use berberine simultaneously
(BB) migration of smooth muscle cell is substantially reduced on (right side) afterwards；Middle row, NE, which is stimulated, to be continued after 24 hours, G- G-protein linked receptors enzyme 2
(GRK2) significantly increase, and berberine (BB) can significantly reduce GRK2 protein phosphorylation level；It is descending, smooth muscle cell warp
After NE is stimulated 1 hour, separate cell membrane and extract memebrane protein, as a result berberine (BB) reduction alpha 1 adrenergic receptor (α 1-
AR effect) is significantly stronger than GRK2 specific inhibitor (G), points out berberine effectively to suppress GRK2 signal paths peace
Sliding Muscle cell contract.
Embodiment
Following examples further illustrate present disclosure, but should not be construed as limiting the invention.Without departing substantially from
In the case of spirit and essence of the invention, the modification and replacement made to the inventive method, step or condition belong to the present invention
Scope.Unless otherwise specified, the conventional meanses that technological means used in embodiment is well known to those skilled in the art.
Embodiment 1
Prevent and treat the effect of pulmonary hypertension and right heart failure
Cell experiment：
It is most normal during right heart failure after stimulating different time through norepinephrine from intact animal arteria pulmonalis smooth muscle cells
See that the Grk2 and LKB1 of high expression are significantly raised, and (CTL) group is significantly reduced after adding jamaicin simultaneously 30 minutes.As a result show
The anti-norepinephrine of jamaicin stimulates the effect of arteria pulmonalis smooth muscle cells to protrude (Fig. 1)
Zoopery：
Choose 20 beasle dogs, determine pulmonary artery blood hydromechanics after, be randomly divided into jamaicin (gavage raise, 0.1g/d,
14 days altogether) and control group (gavage jamaicin sugarcoating layer, wherein without jamaicin, altogether 14 days).Noted at the 14th day in atrium dextrum
Hydrogen monocrotaline (60mg/kg) is shot, is observed 8 weeks, repetition measurement pulmonary artery haemodynamics.As a result：Only 1 animal of jamaicin group
Mean pulmonary arterial pressure reaches 28mmHg, and the mean pulmonary arterial pressure of remaining 9 animal is equal<25mmHg(19±3.0mmHg)；On the contrary, right
It is equal according to 8 animal mean pulmonary arterial pressures of group>26mmHg (28.4 ± 2.1mmHg), 1 animal is 24.6mmHg, and 1 is in addition
24.8mmHg.As a result show, jamaicin, which has, suppresses the effect that dehydrogenation monocrotaline induces pulmonary hypertension.Followed by, award pair
According to a group mean pulmonary arterial pressure power>After 25mmHg 8 animal gavage jamaicins (0.1g/d, altogether 42 days), arteria pulmonalis smooth muscle
Hyperplasia degree is significantly reduced (Fig. 2).
Clinical trial：
6 idiopathic pulmonary hypertension patients, are divided into two groups (every group each 3)：Control group (takes targeting by original dosage
Medicine), jamaicin group (on the basis of original targeted drug, adds jamaicin 0.3g/d, 3 months altogether).Treat after March, it is small
Bark of a cork tree alkali group right ventricular function is significantly improved (Fig. 3), and mean pulmonary arterial pressure is significantly reduced (Fig. 4)
Embodiment 2
Prevent and treat the effect of in-stent restenosis and thrombus in stents
Patient after 100 drug eluting stent placements, is randomly divided into two groups：Control group (not adding jamaicin) and small
Bark of a cork tree alkali group (from postoperative 3rd month when add jamaicin 0.3/d, 6 months altogether), at postoperative 12nd month check coronary artery make
Shadow.As a result：The ratio of control group in-stent restenosis is 14% (N=7), and ISR (4%, p=occurs in jamaicin group only 2
0.035) and stenosis be significantly lower than control group (58 ± 4% couples of 76.3 ± 9%, p=0.029).For 7 in control group again
The oral jamaicin of narrow patient (0.3/d, altogether 6 months), continues follow-up 9 months, and as a result 6 patient's stenosis significantly subtract
Gently (Fig. 5).
Embodiment 3
Prevent and treat the effect of myocardial infarction
30 myocardial infarction model animals, are randomly divided into control group and jamaicin gavage raising group, as a result show jamaicin
(0.3g, 3 times a day, after 3 months) cardiac muscle cell apoptosis significantly mitigates (Fig. 6 left figures), and electron microscope confirms that apoptotic body subtracts
Few (Fig. 6 right figure A-C).Jamaicin treatment group cardiac muscle cell arrangement is more complete.
Embodiment 4
Prevent and treat heart failure caused by ischemic cardiomyopathy
Patient is randomly divided into control group and jamaicin group (0.3g, 3 times a day, after 3 months) after 40 acute myocardial infarction AMIs,
Control group average Left Ventricular LVEF is 41%, and jamaicin group increases and decreases to 53% (p=0.037).Fig. 7 show one it is acute
The 22nd day left ventricle is significantly expanded after Anterior Wall Myocardial Infarction infarct, LVEF is reduced, myocardial contraction is flat (up), warp
The chambers of the heart is reduced, LVEF is dramatically increased, myocardial contractive power is remarkably reinforced (descending) after the jamaicin treatment for spending 3 months.
Embodiment 5
Jamaicin FirebirdTM, including medical cochrome skeleton, 80~100 μm of skeleton thickness are coated with poly- on skeleton
Second lactide (PGLA) or PLA (PLA) degradable membrane, the metallic framework are loaded with jamaicin.By jamaicin and degradable
Film dissolves in ethanol, obtains drug coating solution；Drug coating solution is coated to rack surface；By the support of coating
Vacuum drying solidification, that is, obtain bracket for eluting medicament, carries pharmaceutical quantities 70-180 μ g/mm2.Using and effect referring to Fig. 8~Figure 10.
Smooth muscle cell proliferation and concurrent crux during various dose berberine implantation Medical small-sized porcine coronary 6 months
Really, it see the table below shown：
| <70μg/mm2 | 70-170μg/mm2 | 171-180μg/mm2 | >180μg/mm2 | |
| Size of animal, only | 11 | 26 | 14 | 12 |
| Stent length, mm | 23±5 | 24±6 | 23±6 | 23±5 |
| Stent diameter, mm | 2.52±0.3 | 2.50±0.3 | 2.50±0.3 | 2.50±0.3 |
| Late luminal is lost, mm | 0.20±0.09 | 0.13±0.05 | 0.13±0.06 | 0.13±0.07 |
| Thrombus in stents, % | 0 | 0 | 0 | 4 |
| Death, % | 0 | 0 | 0 | 2 |
Pharmaceutical quantities are carried between 70-180 μ g/mm2Berberine FirebirdTM simultaneously have significantly reduce lumen diameter lose,
Thrombus in stents and the effect of death.Carry pharmaceutical quantities<70μg/mm2When, late luminal, which is lost, significantly increases (p<0.05).
Claims (7)
1. it is coated with release-controlled film on jamaicin FirebirdTM, including medical metal skeleton, skeleton, it is characterised in that the metal bone
Frame or release-controlled film are loaded with jamaicin.
2. jamaicin FirebirdTM according to claim 1, it is characterised in that the metallic framework is cochrome, skeleton
80 ~ 100 μm of thickness.
3. jamaicin FirebirdTM according to claim 1, it is characterised in that the jamaicin on the FirebirdTM carries medicine
Dosage 70-180 μ g/mm2。
4. jamaicin FirebirdTM according to claim 1, it is characterised in that the release-controlled film is degradable membrane.
5. jamaicin FirebirdTM according to claim 4, it is characterised in that the degradable membrane is poly (glycolide-lactide)
（PGLA）Or PLA（PLA）.
6. jamaicin FirebirdTM according to claim 4, it is characterised in that the degradable membrane, which implants 3 days, to be discharged
Total pharmaceutical quantities 25wt.%, the 50wt.% that total pharmaceutical quantities are discharged after 7 days, the 85wt.% that total pharmaceutical quantities are discharged after 28 days.
7. jamaicin FirebirdTM according to claim 4, it is characterised in that degradable in the degradable membrane 60 days.
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| CN201710181676.9A CN107158486A (en) | 2017-03-24 | 2017-03-24 | Jamaicin FirebirdTM |
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