CN108236612A - Combination product for anti-freezing in Percutaneous Coronary Intervention and application thereof - Google Patents
Combination product for anti-freezing in Percutaneous Coronary Intervention and application thereof Download PDFInfo
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- CN108236612A CN108236612A CN201611227828.6A CN201611227828A CN108236612A CN 108236612 A CN108236612 A CN 108236612A CN 201611227828 A CN201611227828 A CN 201611227828A CN 108236612 A CN108236612 A CN 108236612A
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- China
- Prior art keywords
- combination product
- heparin
- molecular weight
- low molecular
- freezing
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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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/727—Heparin; Heparan
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
Abstract
The present invention provides a kind of combination product for anti-freezing in Percutaneous Coronary Intervention, the combination product includes the unfractionated heparin of therapeutically effective amount and the low molecular weight heparin of therapeutically effective amount, the unfractionated heparin and low molecular weight heparin are that respective self-existent reagent state, the unfractionated heparin and the low molecular weight heparin sequential administration in Percutaneous Coronary Intervention operation give subject in need.Combination product provided by the present invention, anti-freezing combination product in more preferable, safer art is provided for clinical PCI arts of selecting a time, so as to reduce patient suffering and inconvenience, is expected to improve patient's prognosis, vast patients with coronary heart disease is benefited, there is important society, science and economic value.
Description
Technical field
Combination product more particularly to a kind of combination for anti-freezing in Percutaneous Coronary Intervention the present invention relates to a kind of anti-freezing
Product.
Background technology
In the past 20 years, calcification score（percutaneous coronary intervention, PCI）Technology is rapidly sent out
Exhibition significantly changes the treatment mode of current coronary heart disease.Success rate, safety and reliability and the prognosis at a specified future date of PCI all obtains
To being obviously improved.The progress of operating technology is not only as, also has benefited from the ancillary drug of perioperative, especially anticoagulation
Object, including unfractionated heparin（unfractioned heparin, UFH）, low molecular weight heparin（low molecular weight
heparin, LMWH）, platelet membrane glycoprotein（GP）The application of II b/, III a receptor antagonists or direct thrombin inhibitor etc..
Rationally using said medicine, patient's prognosis and the safety of PCI arts can be significantly improved.（Cohen M, Diez JE,
Levine GN, et al. Pharmaco invasive management of acute coronary syndrome:
incorporating the 2007 ACC/AHA guidelines: the CATH (cardiac catheterization
and antithrombotic therapy in the hospital) Clinical Consensus Panel Report--
III. J Invasive Cardiol. 2007, 19: 525-538; Casterella PJ, Tcheng JE. Review
of the 2005 American College of Cardiology, American Heart Association, and
Society for Cardiovascular Interventions guidelines for adjunctive
pharmacologic therapy during percutaneous coronary interventions: practical
implications, new clinical data, and recommended guideline revisions. Am
Heart J. 2008, 155:781-790; Moliterno DJ. Advances in antiplatelet therapy
for ACS and PCI. J Interv Cardiol.2008, 21 Suppl 1: S18-S24; Cohen M,
Hoekstra J. The use of adjunctive anticoagulants in patients with acute co
ronary syndrome transitioning to percutaneous coronary intervention. Am J
Emerg Med. 2008; 26:932-941.）Therefore, above-mentioned anticoagulant occupies very important status in PCI technologies,
It can be said that without anti-freezing just without the rapid development of PCI.
Since PCI technologies come out, the UFH as traditional anticoagulant is used guard against in conduit always, in stent with
And endovascular thrombosis.（Niccoli G, Banning AP. Heparin dose during percutaneous
coronary intervention: how low dare we go Heart. 2002, 88:331-334; Marmur JD,
Bullock-Palmer RP, Poludasu S, et al. Avoiding intelligence failur es in the
cardiac catheterization laboratory: Strategies for the safe and rational use
of dalteparin or enoxaparin during percutaneous coronary intervention. J
Invasive Card iol. 2009, 21: 653-664.）But UFH is used for anti-freezing in PCI arts and there is obvious deficiency,
Including：1）Poor bioavailability, dose-effect relationship is poor, and anticoagulation is unstable and unpredictability, it is therefore desirable to which monitoring activation is solidifying
The blood time（ACT）；2）The possibility of heparin-induced thrombocytopenia；3）The fibrin ferment of thrombus cannot be inhibited to be incorporated into；4）Stop
Ischemic event increases after medicine.
In consideration of it, other anticoagulation regimens in PCI arts need to be tried to explore, to obtain safer and more effective anticoagulant effect.In recent years
Come about LWMH（Mainly Enoxaparin）The clinical evidence applied in PCI arts continues to bring out, thus its anti-freezing in PCI arts
Application from scratch, caused great concern.Beneficial exploration is made Enoxaparin in many researchs, by STEEPLE,
SYNERGY and ExTRACT-TIMI 25 are studied（Montalescot G, White HD, Gallo R, Cohen M, Steg
PG, Aylward PE, et al. Enoxaparin versus unfractionated heparin in elective
percutaneous coronary intervention. N Engl J Med 2006, 355: 1006-1017; White
HD, DSc Kleiman NS, Mahaffey KW, et al. Efficacy and safety of enoxaparin
compared with unfractionated heparin in high-risk patients with non–ST-
segment elevation acute coronary syndrome undergoing percutaneous coronary
intervention in the Superior Yield of the New Strategy of Enoxaparin,
Revascularization and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial. Am
Heart J. 2006, 152: 1042-1050；Mehta SR, Granger CB, Eikelboom JW, et al.
Efficacy and safety of fondaparinux versus enoxaparin in patients with acute
coronary syndromes undergoing percutaneous coronary intervention: results
from the OASIS-5 trial. J Am Coll Cardiol. 2007; 50:1742-1751.）, inquired into respectively according to promise
Application of the heparin in ACS patient's emergency PCI and PCI art anti-freezings of selecting a time, makes Enoxaparin obtain the UA/ of 2007ACC/AHA
The Chinese percutaneous coronary intervention guide in NSTEMI guides, STEMI guides and 2009 is recommended, and is selected for UA/NSTEMI and STEMI
Anti-freezing in phase, emergency PCI art.But clinical to Enoxaparin, thrombus problem still has misgivings in the conduit of anti-freezing in PCI arts, therefore
Its scheme applied in PCI arts needs to be advanced optimized.
And so far, Enoxaparin and UFH cross-applications are clearly classified as III of anti-freezing in PCI arts by American-European PCI guides
Class is recommended（Evidence rank B）, i.e. the preoperative patients for having received LMWH anti-freezings of PCI, it is not recommended that cross-application UFH in PCI arts.
（Task Force on Myocardial Revascularization of the European Society of
Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery
(EACTS); European Association for Percutaneous Cardiovascular Interventions
(EAPCI). Guidelines on myocardial revascularization. Eur Heart J. 2010, 31:
2501-2555.）And any research and inquirement there is no to select a time the feasibility of cross-application " LMWH after first UFH- " scheme in PCI arts.
Invention content
Therefore, based on prior art the defects of, the purpose of the present invention is to provide one kind to be used for Percutaneous Coronary Intervention moderate resistance
Solidifying combination product.
To achieve these goals, the present invention provides a kind of combination product for anti-freezing in Percutaneous Coronary Intervention,
In, the combination product includes the unfractionated heparin of therapeutically effective amount and the low molecular weight heparin of therapeutically effective amount, the common liver
Element and low molecular weight heparin are respective self-existent reagent state, and the unfractionated heparin and low molecular weight heparin are in calcification score
Sequential administration gives subject in need in surgical procedure.
According to combination product provided by the invention, wherein, the combination product is kit.
According to combination product provided by the invention, wherein, the low molecular weight heparin is selected from one or more of：According to promise
Heparin（Enoxaparin）, nadroparin calcium and Dalteparin Sodium.Most preferably Enoxaparin.
According to combination product provided by the invention, wherein, the dosage of the unfractionated heparin is calculated as 35 with subject's weight ~
75 U/Kg, preferably 40 ~ 60 U/Kg, most preferably 50U/Kg.
According to combination product provided by the invention, wherein, the dosage of the low molecular weight heparin is calculated with subject's weight
For 0.5 ~ 1.0 mg/Kg, preferably 0.6 ~ 0.8 mg/Kg, most preferably 0.75mg/Kg.
According to combination product provided by the invention, wherein, it is described when subject select a time coronary intervention procedure
The unfractionated heparin in combination product is administered before coronary angiography is carried out gives subject in need, the low molecular weight heparin
Subject in need is given in administration after coronary angiography is carried out and before carrying out coronary intervention procedure.Preferably, coronary angiography
The unfractionated heparin 50U/Kg is injected in the interposing catheter of subject described in forward direction, described in the forward direction of row coronary intervention procedure
The supplement Enoxaparin 0.75mg/Kg in interposing catheter.
According to combination product provided by the invention, wherein, in the combination product, the unfractionated heparin and low molecular weight liver
20 ~ 40 minutes, preferably 30 ~ 35 minutes are divided between plain administration time.
According to combination product provided by the invention, wherein, the combination product further includes specification.
According to combination product provided by the invention, wherein, the unfractionated heparin and low molecular weight heparin are each independently
Ejection preparation.Preferably intravenous formulations, subcutaneous injection formulation or preparation is injected by transcatheter arterial.
The present invention also provides said combination products to prepare for the drug of anti-freezing in Percutaneous Coronary Intervention or medical treatment production
Application in product.
Specifically, can be provided by the present invention for the application method of the combination product of anti-freezing in Percutaneous Coronary Intervention：Coronary artery
It is given before radiography and UFH50U/Kg is injected in the interposing catheter of the subject, determine that row PCI is then preoperative to institute in PCI after radiography
State supplement Enoxaparin 0.75mg/Kg in interposing catheter.
Combination product provided by the present invention for anti-freezing in Percutaneous Coronary Intervention provides more preferably, more for clinic PCI arts of selecting a time
Anti-freezing combination product in the art of safety so as to reduce patient suffering and inconvenience, is expected to improve patient's prognosis, benefits vast coronary heart disease
Patient has important society, science and economic value.
Specific embodiment
It is further illustrated the present invention below by specific embodiment, it should be understood, however, that, these embodiments are only
It is used for specifically describing in more detail, and is not to be construed as limiting the present invention in any form.
This part carries out general description to the material and test method that are arrived used in present invention experiment.Although it is
It is it is known in the art that still the present invention still uses up herein to realize many materials and operating method used in the object of the invention
It may detailed description.It will be apparent to those skilled in the art that within a context, if not specified, material therefor of the present invention and behaviour
It is well known in the art as method.
The reagent used in following embodiment is as follows：
Reagent：
UFH, purchased from thousand red-face role's object pharmaceutical factory of Changzhou；Enoxaparin is purchased from match Norfin, Inc of France.
Embodiment 1
The present embodiment is used to illustrate the combination product and its application method provided by the present invention for anti-freezing in Percutaneous Coronary Intervention,
And the comparison with traditional UFH anticoagulation regimens.
The selected patients with coronary heart disease 1600 for planning to implement the PCI that selects a time, randomized grouping to UFH groups（Control group, n=797）
" low dose of UFH- Enoxaparins " Sequent anti-coagnlation group（Test group, n=803）.After all selected patient's row coronary angiographies determine after
It is continuous to give PCI meddler and enter randomized grouping.Patients with coronary heart disease Baseline Data and the coagulation indexes for participating in the present embodiment 1 are specific
Such as Tables 1 and 2.
First, dosage regimen：
UFH control groups：In injecting UFH3000U in conduit before coronary angiography, determine that row PCI arts then supplement UFH extremely after radiography
Total amount（When containing radiography dosage）100U/Kg.
" low dose of UFH- Enoxaparins " Sequent anti-coagnlation group：Using provided by the present invention for anti-freezing in Percutaneous Coronary Intervention
Combination product, i.e., given before coronary angiography and UFH50U/Kg injected in conduit, determined after radiography row PCI then in conduit supplement according to
Promise heparin 0.75mg/Kg.
2nd, Testing index
Primary Endpoint：Major adverse cardiac event during 30d（MACE）Incidence（Dead, the urgent blood fortune weight of make up one's mind again stalk, target vessel
It builds or TIMI massive haemorrhage）.
Secondary endpoints：Thrombus in conduit in PCI arts, TIMI bleedings in postoperative 48h, 1 year when MACE incidences.
Safety endpoints：Period TIMI massive haemorrhage in hospital.
Bleeding grading（TIMI）Definition be：Massive haemorrhage：Intracranial hemorrhage, bleeding leads to hemoglobin decline >=5g/dl or
HCT declines >=15%；Small bleeding：Spontaneous gross hematuria, spitting blood, apparent bleeding but hemoglobin decline >=3g/dl, but under HCT
＜ 15% drops；Inessential bleeding：Above-mentioned standard is not achieved in bleeding.
Monitoring Indexes：Testing index include PCI is preoperative, in art and postoperative 1h, 6h, Activated partial thromboplastin time for 24 hours
（APTT）, TIMI bleeding rates, thrombus and its dependent event incidence in conduit in art；The MACE of each monitoring time point
Incidence；The success rate at once of PCI operations；And other items during the PCI patient that selects a time is hospitalized and during follow-up are often
Rule check.
3rd, statistical analysis
Data management uses 3.0 typing softwares of EPI DATA, and statistical analysis uses SPSS15.0 statistical softwares.All statisticals
Analysis will carry out under bilateral, 0.05 significance.
Although present invention has been a degree of descriptions, it will be apparent that, in the condition for not departing from the spirit and scope of the present invention
Under, the appropriate variation of each condition can be carried out.It is appreciated that the present invention is not limited to the embodiment, and it is attributed to claim
Range, include the equivalent replacement of each factor.
Claims (10)
1. a kind of combination product for anti-freezing in Percutaneous Coronary Intervention, which is characterized in that the combination product, which includes treatment, to be had
The unfractionated heparin of effect amount and the low molecular weight heparin of therapeutically effective amount, the unfractionated heparin and low molecular weight heparin are respectively independent
Existing reagent state, the unfractionated heparin and the low molecular weight heparin sequential administration in Percutaneous Coronary Intervention operation give in need
Subject.
2. combination product according to claim 1, which is characterized in that the combination product is kit.
3. combination product according to claim 1 or 2, which is characterized in that the low molecular weight heparin is selected from following one kind
It is or a variety of：Enoxaparin, nadroparin calcium and Dalteparin Sodium, most preferably Enoxaparin.
4. combination product according to any one of claim 1 to 3, which is characterized in that the dosage of the unfractionated heparin with
Subject's weight is calculated as 35 ~ 75 U/Kg, preferably 40 ~ 60 U/Kg, most preferably 50 U/Kg.
5. combination product according to any one of claim 1 to 4, which is characterized in that the agent of the low molecular weight heparin
Amount is calculated as 0.5 ~ 1.0 mg/Kg, preferably 0.6 ~ 0.8 mg/Kg, most preferably 0.75 mg/Kg with subject's weight.
6. combination product according to any one of claim 1 to 5, which is characterized in that when subject select a time it is coronal
When arterial intervention is performed the operation, the unfractionated heparin in the combination product be administered before coronary angiography is carried out give it is in need tested
Person, the low molecular weight heparin after coronary angiography is carried out and carry out coronary intervention procedure before administration give it is in need tested
Person；Preferably, 50 U/Kg of unfractionated heparin is injected before coronary angiography into the interposing catheter of the subject, row is coronal dynamic
Supplement 0.75 mg/Kg of Enoxaparin in interposing catheter described in the forward direction of arteries and veins intervention operation.
7. combination product according to any one of claim 1 to 6, which is characterized in that described general in the combination product
It is logical that 20 ~ 40 minutes, preferably 30 ~ 35 minutes are divided between heparin and low molecular weight heparin administration time.
8. combination product according to any one of claim 1 to 7, which is characterized in that the combination product further includes
Bright book.
9. combination product according to any one of claim 1 to 8, which is characterized in that the unfractionated heparin and low molecule
Amount heparin is each independently ejection preparation, preferably intravenous formulations, subcutaneous injection formulation or is injected by transcatheter arterial
Preparation.
10. combination product described in any one of claim 1 to 9 prepare for anti-freezing in Percutaneous Coronary Intervention drug or
Application in medical product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611227828.6A CN108236612A (en) | 2016-12-27 | 2016-12-27 | Combination product for anti-freezing in Percutaneous Coronary Intervention and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611227828.6A CN108236612A (en) | 2016-12-27 | 2016-12-27 | Combination product for anti-freezing in Percutaneous Coronary Intervention and application thereof |
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| Publication Number | Publication Date |
|---|---|
| CN108236612A true CN108236612A (en) | 2018-07-03 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201611227828.6A Pending CN108236612A (en) | 2016-12-27 | 2016-12-27 | Combination product for anti-freezing in Percutaneous Coronary Intervention and application thereof |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101151030A (en) * | 2005-03-29 | 2008-03-26 | 贝林格尔·英格海姆国际有限公司 | Combinations comprising at least one direct thrombin inhibitor for the treatment of thrombosis |
| CN101277693A (en) * | 2005-09-02 | 2008-10-01 | 安万特医药股份有限公司 | Use of enoxaparin for performimg percutaneous coronary intervention |
| WO2013016181A1 (en) * | 2011-07-22 | 2013-01-31 | Paringenix, Inc. | Compositions and methods for anti-coagulation |
-
2016
- 2016-12-27 CN CN201611227828.6A patent/CN108236612A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101151030A (en) * | 2005-03-29 | 2008-03-26 | 贝林格尔·英格海姆国际有限公司 | Combinations comprising at least one direct thrombin inhibitor for the treatment of thrombosis |
| CN101277693A (en) * | 2005-09-02 | 2008-10-01 | 安万特医药股份有限公司 | Use of enoxaparin for performimg percutaneous coronary intervention |
| WO2013016181A1 (en) * | 2011-07-22 | 2013-01-31 | Paringenix, Inc. | Compositions and methods for anti-coagulation |
Non-Patent Citations (3)
| Title |
|---|
| 俞春霞等: "冠状动脉介入治疗中不同肝素的抗凝效果比较", 《中西医结合心脑血管病杂志》 * |
| 王超等: "冠脉介入治疗患者联合应用低分子肝素和普通肝素的抗凝作用探讨", 《中西医结合心血管病杂志》 * |
| 贾三庆等: "冠脉介入治疗患者联合应用低分子肝素和普通肝素的抗凝效果研究", 《全科医学临床与教育》 * |
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