CN108785324A - Lauromacrogol and methotrexate (MTX) are preparing the application in treating Cesarean scar pregnancy drug - Google Patents
Lauromacrogol and methotrexate (MTX) are preparing the application in treating Cesarean scar pregnancy drug Download PDFInfo
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- CN108785324A CN108785324A CN201811062561.9A CN201811062561A CN108785324A CN 108785324 A CN108785324 A CN 108785324A CN 201811062561 A CN201811062561 A CN 201811062561A CN 108785324 A CN108785324 A CN 108785324A
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- lauromacrogol
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- methotrexate
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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
- A61K31/74—Synthetic polymeric materials
- A61K31/765—Polymers containing oxygen
- A61K31/77—Polymers containing oxygen of oxiranes
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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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
Abstract
The present invention provides a kind of Lauromacrogols and methotrexate (MTX) to prepare the application in treating Cesarean scar pregnancy drug, under ultrasound guidance, through inserting needle at the posterior fornix of uterus, puncture needle goes directly in pregnant bursa, after extracting pregnant bursa liquid out, it is inactivated with Lauromacrogol, cause embryo's quick inactivating, then methotrexate (MTX) is injected in pregnant bursa and its periphery multiple spot, it can effectively accelerate trophocyte downright bad by drug combination, be conducive to trophoderm stripping, rapid decrease blood-prostatae barrier, separately area's multi-point injection is enriched in incision periphery muscle layer blood flow with Lauromacrogol, effectively block blood flow around trophoderm, gestation sac and periphery muscle layer blood flow significantly reduce, further decline blood-prostatae barrier, significantly reduce ultrasound guidance uterine curettage massive haemorrhage, notch hemotoncus, the complication such as the perforation of uterus.
Description
Technical field
The present invention relates to technical field of medicine preparation, are controlled in preparation in particular to a kind of Lauromacrogol and methotrexate (MTX)
Treat the application in Cesarean scar pregnancy drug.
Background technology
Cicatricial cyesis after cesarean delivery (cesarean scar pregnancy, CSP) refers to fertilization egg implantation in preceding
A kind of ectopic pregnancy at secondary Cesarean esction uterine incision scar is one and defines in limited time, is only limitted to trimester (≤12 weeks)；Pregnant 12
The middle pregnancy period CSP of Zhou Yihou is then diagnosed as " pregnant in utero, cicatricial cyesis after cesarean delivery, Placenta acrreta ", is such as accompanied with
Placenta previa is then diagnosed as " pregnant in utero, cicatricial cyesis after cesarean delivery, Placenta acrreta, placenta previa state ", arrives
The middle pregnancy period in evening is then Placenta acrreta and placental presentation, that is, forms the so-called dangerous placental presentation of act of violence (pernicious placenta
previa).Due to CSP can cause the palace of the Qing Dynasty perform the operation in and postoperative uncontrollable massive haemorrhage, hysterorrhexis, surrounding device palace damage
Wound, or even excision uterus etc. seriously threaten the healthy reproduction even life of women, have caused great attention clinically.
For cicatricial cyesis after cesarean delivery diagnosis and treatment, mainly there is the following aspects at present：1, trimester CSP conducts
A kind of ectopic pregnancy of specific type, principle of diagnosis and treatment are：Early diagnosis, it is early to terminate, it is early to remove.Early diagnosis refers to there is Cesarean esction history
Women it is pregnant again when should row ultrasonic examination as early as possible exclude CSP.It is built once being diagnosed as CSP and should provide the medicine of terminal pregnancy
View, and pregnant thing is removed as early as possible.2, the basic principle and method that should follow and select as far as possible termination of early pregnancy when terminal pregnancy, with
Reduce damage, as far as possible for the purpose of the fecundity of reservation patient.3, therapy has drug therapy, operative treatment or both
Joint.Uterine arterial embolization (uterine artery embolization, UAE) is the important hand for auxiliary treatment CSP
Section, CSP can more effectively be handled by combining with drug therapy or operative treatment.4, drug therapy, currently, more generally acknowledged medicine
Object is methotrexate (MTX) (methotrexate, MTX), and MTX treats the idicatio of trimester CSP：(1), vital sign is steady, and blood is normal
Rule, hepatic and renal function are normal.(2), it is unwilling or is not suitable for the trimester CS patient of operative treatment.Pregnant week is smaller, and HCG is horizontal
Lower, success rate is higher.(3), II type and III type CSP patient are expert at palace of the Qing Dynasty operation or CSP pregnant things remove preoperative pre- place
Reason can prevent the further development of gestation, reduce the risk of intraoperative hemorrhage in time.(4), blood-prostatae barrier level declines after operative treatment
It increases slowly or again, is not suitable for the patient to perform the operation again, MTX expectant treatments can be used.5, also there is ultrasound guidance gestation sac
Interior local injection (25~50mg) or whole body single dose injection MTX (50mg/m2) etc. Regimen Chemotherapies CSP, result of study show,
No matter MTX or combined U AE is used alone, and treatment CSP has the effect of certain, but treatment total time is long, and has treatment failure
Possibility, success rate is 71%~83%.
In view of this, special propose the present invention.
Invention content
The first object of the present invention is to provide a kind of Lauromacrogol and methotrexate (MTX) and treats Cesarean scar pregnancy preparing
Application in drug has many advantages, such as that drug therapy success rate is high.
In order to realize that the above-mentioned purpose of the present invention, spy use following technical scheme：
A kind of Lauromacrogol and methotrexate (MTX) are preparing the application in treating Cesarean scar pregnancy drug.
Preferably, the Cesarean scar pregnancy includes I type of uterus scar pregnancy Wang, II type and III type.
Preferably, the application, specifically includes following steps：
(1) ultrasound guidance, through inserting needle at the posterior fornix of uterus, puncture needle goes directly in pregnant bursa, and after extracting pregnant bursa liquid out, injection is poly-
Then cinnamic alcohol injects methotrexate (MTX)；
(2) separately with Lauromacrogol area's multi-point injection is enriched in incision periphery muscle layer blood flow.
Preferably, in step (1), the dosage of the Lauromacrogol is less than 5ml.
Preferably, in step (1), the dosage of the Lauromacrogol is 2-5ml.
Preferably, in step (1), the dosage of the methotrexate (MTX) is per kilogram of body weight 1mg.
Preferably, in step (1), the dosage of the methotrexate (MTX) is less than 100mg.
Preferably, in step (2), the dosage of the Lauromacrogol is less than 10ml.
Preferably, in step (2), the multi-point injection specifically includes following steps：Pregnant bursa maximum gauge 1-3cm is used
3ml Lauromacrogols；Pregnant bursa maximum gauge 4-6cm 5ml Lauromacrogols；Pregnant bursa maximum gauge 7-9cm 7m Lauromacrogols.
Preferably, in step (2), strip blood flow signal increases 1-2ml Lauromacrogols, and circular blood flow signals increase 3-4ml
Lauromacrogol.
Compared with prior art, beneficial effects of the present invention are：
Under ultrasound guidance, through inserting needle at the posterior fornix of uterus, puncture needle goes directly in pregnant bursa, after extraction about pregnant bursa liquid, with poly-
Cinnamic alcohol inactivates, and causes embryo's quick inactivating, then injects methotrexate (MTX) in pregnant bursa and its periphery multiple spot, can by drug combination
Effectively to accelerate trophocyte downright bad, be conducive to trophoderm stripping, rapid decrease blood-prostatae barrier, separately with Lauromacrogol in incision periphery flesh
Floor blood flow enriches area's multi-point injection, effectively blocks blood flow around trophoderm, gestation sac and periphery muscle layer blood flow significantly reduce, into one
Step declines blood-prostatae barrier, hence it is evident that reduces ultrasound guidance uterine curettage massive haemorrhage, notch hemotoncus, the complication such as perforation of uterus.
Specific implementation mode
Technical scheme of the present invention is clearly and completely described below in conjunction with specific implementation mode, but ability
Field technique personnel will be understood that following described embodiments are some of the embodiments of the present invention, instead of all the embodiments,
It is merely to illustrate the present invention, and is not construed as limiting the scope of the invention.Based on the embodiments of the present invention, the common skill in this field
The every other embodiment that art personnel are obtained without making creative work belongs to the model that the present invention protects
It encloses.The person that is not specified actual conditions in embodiment, carries out according to conventional conditions or manufacturer's recommended conditions.Agents useful for same or instrument
Production firm person is not specified, is the conventional products that can be obtained by commercially available purchase.
A kind of Lauromacrogol and methotrexate (MTX) are preparing the application in treating Cesarean scar pregnancy drug.
Cesarean section scar (cesarean scar pregnancy, CSP) refer to pregnant bursa, fertilized eggs or embryo nidation in
It is a kind of ectopic pregnancy of specific type on previous anterior uterine wall isthmus notch.As cesarean delivery rate is gradually increasing, uterine incision
Gestation also increases increasingly.Early diagnosis to the disease is the key that determine prognosis, if clinical detected only according to blood-prostatae barrier increases, by palace
When interior gestation row induced abortion or drug abortion, then uterus massive hemorrhage may occur.
Lauromacrogol, Brij30 are colourless clear liquid, have a small amount of foam to generate when shaking.Lauromacrogol is poly-
The bulk pharmaceutical chemicals of cinnamic alcohol injection.Lauromacrogol is also the main effective ingredient of polycinnamic alcohol injection.It is chiefly used in treating in the prior art
Varication.
Methotrexate (MTX), for anti-folic acid class antineoplastic.The product are orange-yellow crystalline powder.Mainly by dihydrofoilic acid
The inhibition of reductase and reach the synthesis for hindering tumour cell, and inhibit the growth and breeding of tumour cell.
In some preferred embodiments of the invention, the Cesarean scar pregnancy includes I type of uterus scar pregnancy Wang, II type
With III type.
I type：(1) gestation sac part implantation is partially or mostly located in uterine cavity at the scar of uterus, even a small number of reach palace
Bottom uterine cavity；(2) gestation sac obviously deform, elongate, lower end it is at an acute angle；(3) mesometrium is thinning between gestation sac and bladder, thickness
>3mm；(4)CDFI：Trophoderm blood flow signal (low-resistance blood flow) is seen at scar.
II type：(1) gestation sac part implantation is partially or mostly located in uterine cavity at the scar of uterus, even a small number of reach
Palace bottom uterine cavity；(2) gestation sac obviously deform, elongate, lower end it is at an acute angle；(3) mesometrium is thinning between gestation sac and bladder, thick
Degree≤3mm；(4)CDFI：Trophoderm blood flow signal (low-resistance blood flow) is seen at scar.
III type：(1) the complete implantation of gestation sac muscle layer and to bladder direction evagination at the scar of uterus；(2) uterine cavity and uterus
It is hollow in neck tube；(3) even mesometrium is obviously thinning between gestation sac and bladder, lacks, thickness≤3mm；(4)CDFI：Scar
Trophoderm blood flow signal (low-resistance blood flow) is seen at trace.
Wherein, there is the characteristics of a kind of special ultrasonic findings CSP, i.e. mass type, ultrasonogram in III type：(1) it is located at son
Mixing echo (being in capsule reality) mass at the hypomere scar of palace, is in class reality sometimes；Mass is swelled to bladder direction；(2) mass
Even the apparent thinning, missing of mesometrium between bladder；(3)CDFI：More rich blood flow signal is seen on mass periphery, can be low-resistance
Blood flow, minority also can rarely seen a little blood flow signal or no blood signal.Mass type is more common in CSP post-abortion (such as commotio retinaes
Or vacuum suction is postoperative) at the scar of uterus caused by Embryo remnants and bleeding.
In some preferred embodiments of the invention, the application specifically includes following steps：
(1) ultrasound guidance, through inserting needle at the posterior fornix of uterus, puncture needle goes directly in pregnant bursa, and after extracting pregnant bursa liquid out, injection is poly-
Then cinnamic alcohol injects methotrexate (MTX)；
(2) separately with Lauromacrogol area's multi-point injection is enriched in incision periphery muscle layer blood flow.
In some preferred embodiments of the invention, in step (1), the dosage of the Lauromacrogol is less than 5ml.
In some preferred embodiments of the invention, in step (1), the dosage of the Lauromacrogol is 2-5ml.
In some preferred embodiments of the invention, in step (1), the dosage of the methotrexate (MTX) is per kilogram of body weight
1mg。
In some preferred embodiments of the invention, in step (1), the dosage of the methotrexate (MTX) is less than 100mg.
In some preferred embodiments of the invention, in step (2), the dosage of the Lauromacrogol is less than 10ml.
In some preferred embodiments of the invention, in step (2), the multi-point injection specifically includes following steps：
Pregnant bursa maximum gauge 1-3cm, with 3ml Lauromacrogols；Pregnant bursa maximum gauge 4-6cm 5ml Lauromacrogols；Pregnant bursa maximum gauge 7-9cm
With 7m Lauromacrogols.
In some preferred embodiments of the invention, in step (2), strip blood flow signal increases 1-2ml Lauromacrogols, ring
Shape blood flow signal increases 3-4ml Lauromacrogols.
Embodiment
1, inspection method：Using GE four-dimension colorful Doppler ultrasound diagnostic apparatus.Transvaginal Ultrasound inspection, to uterus and bilateral
Attachment area carries out routine examination, and observes pregnant bursa or mass size, position at Cesarean esction scar, echo characteristics, form, to scar
Plumule, yolk bag size, the beating of heart pipe, measure mesometrium thickness at scar, observe muscle layer around pregnant bursa inside trace gestation sac
And intralesional blood circumstance, and observe gestation sac and incisional scar and the position relationship of bladder.
2, the scope of application：I type of uterus scar pregnancy Wang, II type ultrasound guidance drug combination interventional treatment.Uterus scar
III type of pregnancy pattern carries out preoperative pretreatment with ultrasound guidance drug combination interventional treatment, then row pregnant thing is removed plus uterus scar
The pregnant neoplasty of trace.
3, therapeutic equipment：GE four-dimension colorful Doppler ultrasound diagnostic apparatus, transvaginal probe, puncture supporter, PTC needles.
Wherein, puncture supporter：The intracavitary puncture supporter of Suzhou Li Pu companies customization；PTC needles：Japanese Ba Guang
4, therapy：
Ultrasound guidance, through inserting needle at the posterior fornix of uterus, puncture needle goes directly in pregnant bursa, after extraction about pregnant bursa liquid, uses 2-5ml
The quick embryo's inactivation of Lauromacrogol of (dosage is the 60% of extraction about pregnant bursa liquid measure, and maximum is no more than 5ml), while in pregnant bursa
Wall construction is destroyed, and then in pregnant bursa and its periphery multiple spot injection dosage, by per kilogram of body weight 1mg calculating, (maximum does not surpass
Cross 100mg) methotrexate (MTX) 2ml, pregnant bursa quick inactivating can be caused by drug combination and form aseptic necrosis, rapid decrease
Blood-prostatae barrier separately enriches area's multi-point injection (according to pregnant bursa size and incision blood flow signal with Lauromacrogol in incision periphery muscle layer blood flow
It is prepared, pregnant bursa maximum gauge 1-3cm 3ml, 4-6cm 5ml, 7-9cm 7ml, dotted blood flow signal does not increase, strip
Blood flow signal increases 1-2ml, and circular blood flow signals increase 3-4ml, injects maximum maximum dose and should be 10ml), trophoderm is broken
It is bad, around gestation sac the blood flow short time significantly reduce, wait for that blood-prostatae barrier is decreased obviously 50% or less and gestation sac Peripheral blood lumen is aobvious subtracts
Row ultrasound guidance uterine curettage again after few.The villus and decidua sample tissue tissue that denaturation is sucked out send disease inspection, pathology to turn out to be pregnant
It is pregnent tissue.
Test example
Experiment 1:Under ultrasound guidance, through inserting needle at the posterior fornix of uterus, puncture needle goes directly in pregnant bursa, extraction about pregnant bursa liquid
Afterwards, with 5mg methotrexate dilution rinse in pregnant bursa and carry out embryo's inactivation, then injected in pregnant bursa and its periphery multiple spot
The methotrexate (MTX) of per kilogram of body weight 1mg, during treatment, vagina color ultrasound monitors blood flow signal around gestation sac or mass
Variation, periodic detection blood-prostatae barrier is horizontal, goes again after blood-prostatae barrier is decreased obviously 50% or less and gestation sac Peripheral blood stream significantly reduces
Ultrasound guidance uterine curettage.The villus and decidua sample tissue tissue that denaturation is sucked out send disease inspection, pathology to turn out to be pregnant tissue.
Experiment 2:Ultrasound guidance, through inserting needle at the posterior fornix of uterus, puncture needle goes directly in pregnant bursa, after extraction about pregnant bursa liquid,
With the Lauromacrogol of 2-4ml, quick embryo inactivates, while being destroyed to pregnant bursa interior wall construction, then more in pregnant bursa and its periphery
Point injection per kilogram of body weight 1mg methotrexate (MTX) 2ml, can cause pregnant bursa quick inactivating by drug combination and to form aseptic bad
Extremely, rapid decrease blood-prostatae barrier separately enriches area's multi-point injection in incision periphery muscle layer blood flow with Lauromacrogol, is destroyed to trophoderm,
The blood flow short time significantly reduces around gestation sac, wait for blood-prostatae barrier be decreased obviously 50% or less and gestation sac Peripheral blood stream significantly reduce
Row ultrasound guidance uterine curettage again afterwards.The villus and decidua sample tissue tissue that denaturation is sucked out send disease inspection, pathology to turn out to be gestation
Tissue.
Comparing result is as shown in table 1.
Table 1
Test result shows under ultrasound guidance, and through inserting needle at the posterior fornix of uterus, puncture needle goes directly in pregnant bursa, and extraction is about
It after pregnant bursa liquid, is inactivated with Lauromacrogol, causes embryo's quick inactivating, then inject methotrexate (MTX) in pregnant bursa and its periphery multiple spot,
It can effectively accelerate trophocyte downright bad by drug combination, be conducive to trophoderm stripping, rapid decrease blood-prostatae barrier, separately with poly- osmanthus
Alcohol enriches area's multi-point injection in incision periphery muscle layer blood flow, effectively blocks blood flow, gestation sac and periphery muscle layer blood around trophoderm
Stream significantly reduces, and further declines blood-prostatae barrier, hence it is evident that reduces ultrasound guidance uterine curettage massive haemorrhage, notch hemotoncus, perforation of uterus etc.
Complication.
Lauromacrogol and methotrexate (MTX) provided herein is preparing the application in treating Cesarean scar pregnancy drug, medicine
Object success rate is high.
Although illustrate and describing the present invention with specific embodiment, it will be appreciated that the above various embodiments is only used
To illustrate technical scheme of the present invention, rather than its limitations；It will be understood by those of ordinary skill in the art that：Without departing substantially from this hair
It, can be with technical scheme described in the above embodiments is modified, or to wherein in the case of bright spirit and scope
Some or all of technical characteristic carries out equivalent replacement；And these modifications or replacements, do not make the essence of corresponding technical solution
It departs from the scope of the technical solutions of the embodiments of the present invention；It is, therefore, intended that including belonging to the present invention in the following claims
All these substitutions and modifications in range.
Claims (10)
1. a kind of Lauromacrogol and methotrexate (MTX) are preparing the application in treating Cesarean scar pregnancy drug.
2. application according to claim 1, which is characterized in that the Cesarean scar pregnancy includes uterus scar pregnancy Wang I
Type, II type and III type.
3. application according to claim 1, which is characterized in that specifically include following steps：
(1) ultrasound guidance, through inserting needle at the posterior fornix of uterus, puncture needle goes directly in pregnant bursa, after extracting pregnant bursa liquid out, injects poly- osmanthus
Then alcohol injects methotrexate (MTX)；
(2) separately with Lauromacrogol area's multi-point injection is enriched in incision periphery muscle layer blood flow.
4. application according to claim 3, which is characterized in that in step (1), the dosage of the Lauromacrogol is less than 5ml.
5. application according to claim 4, which is characterized in that in step (1), the dosage of the Lauromacrogol is 2-5ml.
6. application according to claim 3, which is characterized in that in step (1), the dosage of the methotrexate (MTX) is per public
Jin weight 1mg.
7. application according to claim 6, which is characterized in that in step (1), the dosage of the methotrexate (MTX) is less than
100mg。
8. application according to claim 3, which is characterized in that in step (2), the dosage of the Lauromacrogol is less than
10ml。
9. application according to claim 3, which is characterized in that in step (2), the multi-point injection, specifically include with
Lower step：Pregnant bursa maximum gauge 1-3cm, with 3ml Lauromacrogols；Pregnant bursa maximum gauge 4-6cm 5ml Lauromacrogols；Pregnant bursa is maximum straight
Diameter 7-9cm 7m Lauromacrogols.
10. application according to claim 9, which is characterized in that in step (2), it is poly- that strip blood flow signal increases 1-2ml
Cinnamic alcohol, circular blood flow signals increase 3-4ml Lauromacrogols.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105412009A (en) * | 2015-12-17 | 2016-03-23 | 张淑珍 | Application of lauromacrogol injection as drug for curing cesarean scar pregnancy |
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2018
- 2018-09-12 CN CN201811062561.9A patent/CN108785324A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105412009A (en) * | 2015-12-17 | 2016-03-23 | 张淑珍 | Application of lauromacrogol injection as drug for curing cesarean scar pregnancy |
Non-Patent Citations (1)
| Title |
|---|
| 孟迪云 等: "超声引导下聚桂醇联合甲氨蝶呤孕囊注射治疗剖宫产瘢痕妊娠的疗效观察", 《浙江医学》 * |
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Application publication date: 20181113 |