CN105769859A - Medicine composition for treating after-radiotherapy skin injuries of cervical cancer patient and application of medicine composition - Google Patents
Medicine composition for treating after-radiotherapy skin injuries of cervical cancer patient and application of medicine composition Download PDFInfo
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- CN105769859A CN105769859A CN201610130909.8A CN201610130909A CN105769859A CN 105769859 A CN105769859 A CN 105769859A CN 201610130909 A CN201610130909 A CN 201610130909A CN 105769859 A CN105769859 A CN 105769859A
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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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4192—1,2,3-Triazoles
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Abstract
The invention discloses a medicine composition for treating the after-radiotherapy skin injuries of a cervical cancer patient and application of the medicine composition.The medicine composition is prepared from active components and auxiliaries.The active components include 5-(N-2-phenylethylamino)-2-(4-methoxyphenyl)-2H-benzotriazole.The phagocytosis and chemotaxis functions of neutral granular cells can be improved, the treatment effect on treating the after-radiotherapy skin injuries of the cervical cancer patient through external application is remarkable, and the composition is easy to operate, convenient to use, free of adverse events, safe and reliable.
Description
Technical field
The invention belongs to pharmaceutical technology field, be specifically related to a kind of treat the medicine group of skin injury after radiotherapy patients with cervix carcinoma
Compound and application thereof.
Background technology
Cervical carcinoma is the malignant tumour being primary in uterine cervix, ranks first in female sex organ malignant tumour, and operation is
The main method for the treatment of cervical carcinoma, but be only used in early days (0 phase or Ia phase), therefore radiotherapy is again cervical carcinoma
One of critical treatment means.The radiotherapy of cervical carcinoma is typically after irradiating radical-ability dosage 1/3, and irradiation area is the most permissible
Erythema, sepage and breakage occur, due to the anatomical structure that perineum is unique, perineal skin is moist, thin tender, many
Gauffer, adds that the friction of stool and urine and clothing easily causes infection.Along with the increase of intergal dose, the reaction of above-mentioned position adds
Heavy then serious moist reaction can be occurred to form ulceration, if preventing the most not in time and processing, once formation ulcer and sense
Dye, can affect whole radiotherapy process, even TD, there is also irradiation area skin prolonged ulcer late period not
More, considerable distress will be caused to patient.
CN105218532A discloses a kind of benzotriazole micromolecular compound or its pharmaceutically acceptable acid addition
Salt, also disclose this benzotriazole micromolecular compound or its pharmaceutically acceptable acid-addition salts preparation treatment by
The various malignant growths that cause in RAS gene mutation, shift and medical usage in the disease medicament such as recurrence, so
And it does not disclose this compounds in terms for the treatment of after radiotherapy patients with cervix carcinoma skin injury or treatment diabetic complication
Biologically active.
Summary of the invention
In view of the deficiencies in the prior art, it is an object of the invention to provide one and treat skin injury after radiotherapy patients with cervix carcinoma
Pharmaceutical composition and application.
The object of the present invention is achieved like this:
A kind of treat the pharmaceutical composition of skin injury after radiotherapy patients with cervix carcinoma, active component and auxiliary material be prepared from,
Described active component includes 5-(N-2-phenylethylcarbamate)-2-(4-methoxyphenyl)-2H-BTA.
Preferably, the pharmaceutical composition of skin injury, wherein said activity after treatment radiotherapy patients with cervix carcinoma described above
Composition is made up of 5-(N-2-phenylethylcarbamate)-2-(4-methoxyphenyl)-2H-BTA.
Compound 5-(N-2-phenylethylcarbamate)-2-(4-methoxyphenyl)-2H-BTA involved in the present invention, its hydrogen
Modal data is:1HNMR (DMSO, 300MHz): δ 8.13 (d, J=9.0Hz, 2H), 7.69 (d, J=9.0Hz, 1H),
7.32 (s, 3H), 7.23-7.22 (m, 1H), 7.13 (m, 2H), 7.03 (dd, J=0.3,0.3Hz, 1H), 6.61 (s,
1H), 6.33-6.32 (m, 1H), 3.83 (s, 3H), 3.62-3.36 (m, 2H), 2.96-2.92 (m, 2H).
It is further preferred that the pharmaceutical composition of skin injury after treating radiotherapy patients with cervix carcinoma as mentioned above, wherein said
Therapeutic combination be topical administration formulations, described topical administration formulations is selected from gel, ointment, liniment and lotion
One.
The most preferably, after treatment radiotherapy patients with cervix carcinoma, the pharmaceutical composition of skin injury is liniment as mentioned above,
And drug concentration is 5～50mg/mL, further preferred drug concentration is 10～30mg/mL.
After total body radiation damage, contraction of wounds slows down, and the average healing extends, and wound stretching intensity significantly reduces.This
Invention medicine has the growth of promotion new granulation tissue, effect of the repairing ulcer surface of a wound, to promote contraction of wounds, shortens flat
All healing times, increase surface of a wound tensile strength.It addition, must during in Patients During Radiotherapy, Changes of Radiation Damaged Skin is Patients During Radiotherapy
The complication so occurred, has become one of restriction patient's principal element smoothly completing radiotherapy.Medicine of the present invention can improve
Neutrophil phagocytosis and Chemotaxis Function, evident in efficacy by skin injury after external application for curing irradiation for cervical cancer, and operation letter
Single, easy to use, adverse events does not occurs, safe and reliable.Therefore, the present invention also provides for a kind of pharmaceutical applications, it may be assumed that
The skin injury after preparation treatment cancer radiation of 5-(N-2-phenylethylcarbamate)-2-(4-methoxyphenyl)-2H-BTA
Medicine in application.Preferably, described cancer is cervical carcinoma.
Detailed description of the invention
The following is the specific embodiment of the present invention, technical scheme is done to be described further, but the present invention
Protection domain is not limited to these embodiments.Every change without departing substantially from present inventive concept or equivalent replacement are included in this
Within bright protection domain.
The preparation of embodiment 1:5-(N-2-phenylethylcarbamate)-2-(4-methoxyphenyl)-2H-BTA
(1) P-nethoxyaniline (2.48g, 20.14mmol) is dissolved in the aqueous hydrochloric acid solution (4M) of 48ml, at ice
Natrium nitrosum (1.67g, 24.17mmol) is added, after reacting half an hour, by Amcide Ammate (3.16g) at 0 DEG C under the conditions of bath
Under be slowly added in system and continue stir half an hour.With sodium acetate, the pH of solution is adjusted to 5-6, in condition of ice bath
Lower o-phenylendiamine dihydrochloride (3.33g, 18.42mmol) is joined in reaction system, be stirred overnight.TLC detects
After reaction completely, with sodium hydroxide solution regulation to pH more than 14, extract with ethyl acetate and water, merge organic
Phase, decompression distillation, obtain the crude product azo-compound being dried.The pyridinium dissolution of azo-compound 40ml, by 10g
Anhydrous cupric sulfate joins in 60ml concentrated ammonia liquor/water (v/v=1/1) mixed solution, and mixture refluxes under oil bath, directly
To reaction completely.
(2) reactant liquor by cooling adds the water of excess, extracts with ethyl acetate and water, merges organic phase, subtracts
Pressure distillation, the crude product BTA amine obtained separates through column chromatography, obtains pure 2-(4-methoxyphenyl)-5-ammonia
Base-2H-BTA 2.52g.
(3) by 2-(4-methoxyphenyl)-5-amino-2H-BTA (0.42g, 1.74mmol), phenylacetic acid (0.24g,
1.74mmol), HOBt (0.26g, 1.92mmol) and EDC.HCl (0.43g, 2.24mmol) is dissolved in DMF (10ml)
In, it is stirred under 50-60 DEG C of oil bath, detects with TLC, until reaction is completely.Add the water of excess, use
Ethyl acetate and water extract, and merge organic phase, decompression distillation, obtain crude product, separate by column chromatography, obtain
Pure N-(2-(4-methoxyphenyl)-2H-BTA-5-amino)-2-phenyl-acetamides 0.57g, productivity 91%.Then will
N-(2-(4-methoxyphenyl)-2H-BTA-5-amino)-2-phenyl-acetamides (0.57g, 1.59mmol) is under condition of ice bath
Under be dissolved in THF (10ml), be dividedly in some parts lithium aluminium hydride reduction (0.60g, 15mmol), when producing to there is no bubble, remove
Deicing is bathed, and refluxes in oil bath, and TLC carries out detecting until reacting complete.Add the ethyl acetate of excess, use
Ethyl acetate and water extract, and merge organic phase, decompression distillation, obtain crude product, separate by column chromatography, obtain
Pure 5-(N-2-phenylethylcarbamate)-2-(4-methoxyphenyl)-2H-BTA 0.32g, productivity 59%.1HNMR (DMSO, 300MHz): δ 8.13 (d, J=9.0Hz, 2H), 7.69 (d, J=9.0Hz, 1H), 7.32 (s,
3H), 7.23-7.22 (m, 1H), 7.13 (m, 2H), 7.03 (dd, J=0.3,0.3Hz, 1H), 6.61 (s, 1H), 6.33-6.32 (m,
1H), 3.83 (s, 3H), 3.62-3.36 (m, 2H), 2.96-2.92 (m, 2H).
Embodiment 2:5-(N-2-phenylethylcarbamate)-2-(4-methoxyphenyl)-2H-BTA (hereinafter referred to as RS042) medicine
The preparation of liquid
Preparation method: at normal temperatures and pressures, weighs propane diols 10g, is dissolved in appropriate distilled water, according still further in prescription
The proportioning of each component is separately added into RS042 1.5g, Sodium Benzoate 0.01g, is stirred to dissolve, and finally adds distilled water extremely
100ml, is sufficiently stirred for, mixing, and regulation pH to 7.0, canned simultaneously, and finished product is checked to obtain in sealing.
Embodiment 3:RS042 liquid is to the effectiveness study of skin injury patient after irradiation for cervical cancer
Cervical cancer patient 52 example, wherein squama cancer 23 example, gland cancer 29 example.It is randomly divided into observation group 26 example, control group 26
Example, 25 years old observation group's age～59 years old, average (44.2 ± 9.6) year, 24 years old control group age～60 years old, average (45.7
± 8.5) year.Two groups of ages compare, pathological comparing difference without conspicuousness, there is comparativity.All patients all use
Linear accelerator x-ray external exposure, B point DT40Gy～50Gy/20～25 times/4～5 weeks；Intracavitary afterloading therapy, adopts
With 198Ir afterloading unit intracavitary radiotherapy, A point DT4 dosage 30～36Gy/5～6 times.Often group case does introduction on discharge: protect
Holding perineum cleaning, be dried, forbid embrocating excitant and oiliness medicine, treatment all starts after dermoreaction occurs, right
Use 0.1% bromogeramine or normal saline flushing perineum according to group, 3 times/d, continue to radiotherapy to terminate.Observation group is external application
RS042 liquid, 3 times/d, operating procedure: take sterile treatment bowl and pour RS042 liquid into (by the prescription work of embodiment 2
Skill prepare) 10～20mL, cover after sterile gauze is impregnated with solution on perineal region skin, surrounding exceed ulceration scope 1～
2cm, then cover that one layer of sterile gauze is fixing can prevent drug volatilization from becoming dry, can prevent again liquid from staining clothing, reservation 15～
20min/ time, 3 times/d, continue to radiotherapy to terminate.During medication, every day notes observing local skin situation, pain relief
Situation, ulceration healing and patient have no adverse reaction.
After two groups of treatments terminate, press RTOG grade scale according to cancer radiation therapy association skin acute radiation injury and pass judgment on
As follows:
Effective: after treatment, 7d inner skin ulcer heals completely, and engorgement pain disappears substantially；
Effective: after treatment, 7d inner skin ulcer is obviously reduced, and engorgement pain disappears substantially；
Minor effect: after treatment, 7d inner skin ulcer area, hyperemia, pain are not improved；14d inner skin ulcer area,
Congested, pain has improvement；
Invalid: after treatment, 14d inner skin ulcer area, hyperemia, pain are not improved.
General curative effect comparative result sees table 1.Result shows, after the treatment of observation group skin acute radiation injury total effectively
Rate (effective+effectively) and it is 96.2%, control group is 61.5%.The evident in efficacy of observation group is better than control group.
1 liang of table group general curative effect compares
Claims (7)
1. treat the pharmaceutical composition of skin injury after radiotherapy patients with cervix carcinoma for one kind, it is characterised in that: by active component
Being prepared from auxiliary material, described active component includes 5-(N-2-phenylethylcarbamate)-2-(4-methoxyphenyl)-2H-benzo
Triazole.
The most according to claim 1, the pharmaceutical composition of skin injury after treatment radiotherapy patients with cervix carcinoma, its feature exists
In: described active component is made up of 5-(N-2-phenylethylcarbamate)-2-(4-methoxyphenyl)-2H-BTA.
The pharmaceutical composition of skin injury after treatment radiotherapy patients with cervix carcinoma the most according to claim 1 or claim 2, it is special
Levy and be: described pharmaceutical composition is topical administration formulations, described topical administration formulations selected from gel, ointment,
Liniment and the one of lotion.
The most according to claim 3, the pharmaceutical composition of skin injury after treatment radiotherapy patients with cervix carcinoma, its feature exists
In: described pharmaceutical composition is liniment, and drug concentration is 5～50mg/mL.
The most according to claim 3, the pharmaceutical composition of skin injury after treatment radiotherapy patients with cervix carcinoma, its feature exists
In: described pharmaceutical composition is liniment, and drug concentration is 10～30mg/mL.
6.5-(N-2-phenylethylcarbamate)-2-(4-methoxyphenyl)-2H-BTA is skin after preparation treatment cancer radiation
Application in the medicine of skin damage.
Application the most according to claim 4, it is characterised in that: described cancer is cervical carcinoma.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610130909.8A CN105769859B (en) | 2016-03-09 | 2016-03-09 | It is a kind of to treat the pharmaceutical composition of skin injury and its application after radiotherapy patients with cervix carcinoma |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610130909.8A CN105769859B (en) | 2016-03-09 | 2016-03-09 | It is a kind of to treat the pharmaceutical composition of skin injury and its application after radiotherapy patients with cervix carcinoma |
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| Publication Number | Publication Date |
|---|---|
| CN105769859A true CN105769859A (en) | 2016-07-20 |
| CN105769859B CN105769859B (en) | 2018-06-26 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610130909.8A Expired - Fee Related CN105769859B (en) | 2016-03-09 | 2016-03-09 | It is a kind of to treat the pharmaceutical composition of skin injury and its application after radiotherapy patients with cervix carcinoma |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130035304A1 (en) * | 2010-01-29 | 2013-02-07 | Walensky Loren D | Small molecules for the modulation of mcl-1 and methods of modulating cell death, cell division, cell differentiation and methods of treating disorders |
| US20150284387A1 (en) * | 2014-04-04 | 2015-10-08 | The Regents Of The University Of Michigan | Small molecule inhibitors of mcl-1 and uses thereof |
| CN105218532A (en) * | 2015-10-16 | 2016-01-06 | 华东师范大学 | Benzotriazole compounds, preparation method and its medicinal use |
-
2016
- 2016-03-09 CN CN201610130909.8A patent/CN105769859B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130035304A1 (en) * | 2010-01-29 | 2013-02-07 | Walensky Loren D | Small molecules for the modulation of mcl-1 and methods of modulating cell death, cell division, cell differentiation and methods of treating disorders |
| US20150284387A1 (en) * | 2014-04-04 | 2015-10-08 | The Regents Of The University Of Michigan | Small molecule inhibitors of mcl-1 and uses thereof |
| CN105218532A (en) * | 2015-10-16 | 2016-01-06 | 华东师范大学 | Benzotriazole compounds, preparation method and its medicinal use |
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| CN105769859B (en) | 2018-06-26 |
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