CN108478554A - Purposes of the allyl isothiocyanate in the drug for preparing treatment functional pituitary adenoma - Google Patents
Purposes of the allyl isothiocyanate in the drug for preparing treatment functional pituitary adenoma Download PDFInfo
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- CN108478554A CN108478554A CN201810476282.0A CN201810476282A CN108478554A CN 108478554 A CN108478554 A CN 108478554A CN 201810476282 A CN201810476282 A CN 201810476282A CN 108478554 A CN108478554 A CN 108478554A
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- allyl isothiocyanate
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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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/26—Cyanate or isocyanate esters; Thiocyanate or isothiocyanate esters
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Abstract
Present disclose provides purposes of the allyl isothiocyanate in the drug for preparing treatment functional pituitary adenoma.Through the above technical solutions, use of the disclosure by allyl isothiocyanate, can effectively inhibit the cell Proliferation of prolactin pituitary MMQ on a cellular level, it is in apparent time dependence and dose dependent；At the same time, allyl isothiocyanate can significantly induce MMQ apoptosis, and the tumour growth of tumor-bearing mice can be effectively inhibited in animal model level and extends the life cycle of tumor-bearing mice；Therefore the disclosure provides a kind of new solution by the use of allyl isothiocyanate for the treatment of prolactin pituitary.
Description
Technical field
This disclosure relates to biomedicine field, and in particular, to allyl isothiocyanate is preparing treatment functional pituitary
Purposes in the drug of adenoma.
Background technology
Functional pituitary adenoma includes prolactin pituitary, somatotropinoma and ACTH adenomas etc.；Prolactin pituitary
(prolactinoma) it is most common functional pituitary adenoma, accounts for about the 40%-45% of adult's pituitary function gonadoma.Hypophysis
The main clinical manifestation of prolactin pituitary is hypogonadism, can secrete a large amount of prolactin(PRLs, women can generate amenorrhoea, lactation,
Infertile equal clinical manifestations.Male can lead to sexual disorder, infertility, and surrounding tissue can be invaded when serious, cause under the eyesight visual field
The even threat to life such as drop, headache, seriously affects quality of life of patients.The exact pathogenesis of prolactin pituitary is not complete so far
It is complete clear.
Dopamine-receptor stimulant is the preferred option of prolactin pituitary treatment.Although the reversible most of trouble of drug therapy
The clinical symptoms of person keep prolactin(PRL horizontal normal and reduce gross tumor volume, but still have some shortcomings, as most patients need to grow
Phase medication is not resistant to side effects of pharmaceutical drugs and tumour to dopamine agonist drug resistance etc..Therefore, it explores and is directed to prolactin(PRL gland
The treatment new drug of tumor is of great significance.
Invention content
The purpose of the disclosure is to improve the treatment level of prolactin pituitary, provides a kind of new side treating prolactin pituitary
Case.
To achieve the goals above, present disclose provides allyl isothiocyanates to prepare treatment functional pituitary adenoma
Purposes in drug.
Through the above technical solutions, use of the disclosure by allyl isothiocyanate, it on a cellular level can be effective
The cell Proliferation for inhibiting prolactin pituitary MMQ, be in apparent time dependence and dose dependent；At the same time, different sulphur cyanogen
Allyl propionate can significantly induce MMQ apoptosis, and tumor-bearing mice can be effectively inhibited in animal model level
Tumour growth and extend the life cycle of tumor-bearing mice；Therefore the disclosure is lactation by the use of allyl isothiocyanate
The treatment of plain adenoma provides a kind of new solution.
Other feature and advantage of the disclosure will be described in detail in subsequent specific embodiment part.
Description of the drawings
Attached drawing is for providing further understanding of the disclosure, and a part for constitution instruction, with following tool
Body embodiment is used to explain the disclosure together, but does not constitute the limitation to the disclosure.In the accompanying drawings：
Fig. 1 is the cytologic experiment result figure that 15 kinds of compounds carry out GH3 cells.
Fig. 2 is the cytologic experiment result figure that 15 kinds of compounds carry out MMQ cells.
Fig. 3 is the cytologic experiment result figure that 6 kinds of compounds carry out GH3 cells.
Fig. 4 is the cytologic experiment result figure that 6 kinds of compounds carry out MMQ cells.
Fig. 5 is the result figure that allyl isothiocyanate inhibits prolactinoma MMQ cell Proliferations.
Fig. 6 is the result figure of allyl isothiocyanate induced lactation element tumor MMQ Apoptosis.
Fig. 7 is the result figure of the animal model experiment of the allyl isothiocyanate inhibition prolactinoma MMQ in embodiment 3.
Specific implementation mode
The specific implementation mode of the disclosure is described in detail below in conjunction with attached drawing.It should be understood that this place is retouched
The specific implementation mode stated is only used for describing and explaining the disclosure, is not limited to the disclosure.
Present disclose provides purposes of the allyl isothiocyanate in the drug for preparing treatment functional pituitary adenoma.
Allyl isothiocyanate is particularly suitable for treating prolactin pituitary, therefore in such use, the functionality
Pituitary adenoma is preferably prolactin pituitary.
Wherein, in order to enable the use of the drug is safer, it is preferable that allyl isothiocyanate in the drug
Content is 0.1-200mg/g.
Wherein, in order to enable the drug is more convenient to use, it is preferable that the dosage form of the drug is peroral dosage form, more
Can be specifically pill, tablet, powder or capsule.The pill can be the water-bindered pill, cream ball, starched pill, wax-wrapped pill or condensed pill.
The tablet can be plain piece, sugar coated tablet, enteric coatel tablets, suck piece, chewable tablets, effervescent tablet or control releasing piece.The capsule
Can be hard capsule or soft capsule.The hard capsule can be instant capsule, freeze-drying capsule, magnetic capsule, dual chamber capsule,
Capsulae enterosolubilis, spansule, implant capsule, aerosol capsule, effervesce capsule.The soft capsule can be quick acting capsule, skeleton glue
Capsule, spansule or coating angle capsule.
Wherein, as a reference, the dosage of allyl isothiocyanate is adult per kg body weight 1-100mg.
Wherein, the entitled Allylisothiocyante of English of allyl isothiocyanate, shown in structure such as formula (1)；
Present invention be described in more detail by the following examples.
Embodiment 1
Compare antitumous effect in 35 kinds of extracts, selects 15 kinds of compounds and carry out cytologic experiment.In GH3 and MMQ
The drug concentration of various dose, MTS experiments is used to show that 6 kinds of drugs have the function of inhibiting cell Proliferation in cell line, as a result such as
Shown in Fig. 1-Fig. 4, there are 3 kinds to what two kinds of cells had an inhibiting effect, be Allylisothiocyante (24 inhibiting rates respectively
35%), Tangeretin (24 hours inhibiting rates 38.4%) and Xanthohumol (24 hours inhibiting rates 24%)；There are 3 kinds of drugs
Have the function of promoting pituitary adenoma cells proliferation, wherein Luteolin effects most apparent.Annexin V methods detect drug-treated
The occurred level of apoptosis afterwards finds that 1 μM of Allylisothiocyante is handled 24 hours：GH3 apoptosis rates are 16.4%,
MMQ apoptosis rates are 17.4%；1 μM of Tangeretin is handled 24 hours：GH3 apoptosis rates are 13.7%, MMQ cells
Apoptosis rate is 14.6%.
Embodiment 2
Allyl isothiocyanate is configured to 10mM storing solutions with DMSO, and the used time is diluted to various concentration with DMSO again.Lactation
Plain tumor MMQ cell suspension cultures are in DEME culture solutions (containing 2.5% fetal calf serum, 12.5% horse serum, 1.176g/L
Sodium bicarbonate), in containing 5% carbon dioxide, after being cultivated 48 hours in 37 DEG C of incubator, trypan blue measures cell viability
>99%, replacement culture solution is the DEME culture solutions containing 15% fetal calf serum, and liquid is changed 1 time per 48h, is passed on 1 time within 72 hours.
By the MMQ cells of exponential phase, cell is adjusted a concentration of 5 × 10 with culture solution4/ml.Cell is put into 96
In orifice plate, per 200 μ l of hole.Culture be separately added into various concentration (0,0.1,1,10 μM) allyl isothiocyanate afterwards for 24 hours, respectively after
After 24,48 and 72h of continuous culture, the MTS of 40 μ l is added per hole, continues at 37 DEG C of culture 4h.It is 490nm that wavelength is measured under microplate reader
Locate light absorption value.Inhibiting rate of the allyl isothiocyanate to MMQ cells according to the following formula.Inhibiting rate (%)=(control group OD-
Dosing group OD)/control group OD × 100%.It is repeated 3 times, is averaged.The results are shown in Figure 5.
The MMQ cells of logarithmic growth phase are inoculated in 6 orifice plates, per hole cell 1.5 × 105It is a.After for 24 hours, respectively
Various concentration (0,0.1,1,10 μM) allyl isothiocyanate is added, continues after cultivating 72h, is collected by centrifugation after cell through PBS weights
It is centrifuged after outstanding, it is 1 × 10 to adjust cell concentration6·mL-1(1 × Binding Buffer are resuspended), adds 5 μ L Annexin V-
Mixing in FITC and 10 μ L PI to 500 μ L cell suspensions, flow cytometer detects after room temperature is protected from light 15min.With early stage
The sum of apoptosis and late apoptic ratio are total apoptosis rate.The results are shown in Figure 6.
For statistical analysis with SPSS 17.0, experimental data is indicated with means standard deviation (mean ± SD), sample between each group
This mean value uses one-way analysis of variance (One-way ANOVA), with p<0.05 is significant difference.
As a result it shows：MTS is the experimental results showed that allyl isothiocyanate can significantly inhibit the increasing of prolactinoma MMQ cells
It grows.Compared with the control group, the MMQ cell survival rates through 0.1,1,10 μM of concentration allyl isothiocyanate processing significantly reduce.Such as
Shown in Fig. 5, within the same time, with the increase of allyl isothiocyanate concentration, inhibit MMQ cel l proliferations stronger.
Under same concentration, allyl isothiocyanate inhibition MMQ ability of cell proliferation extends at any time also to be gradually increased.It should be the result shows that different
Allyl sulfocyanate can significantly inhibit the proliferative capacity of newborn plain tumor MMQ cells, and inhibiting effect is in dose dependent and time
Dependence.
Phosphatidylserine (PS) is located on the inside of human cell membrane, and PS is overturn to cell membrane surface when early apoptosis,
Annexin V can be specifically bound with the PS of cell membrane surface, therefore available flow cytomery FITC (fluorescein) marks
The recombination Annexin V of note measure apoptosis rate, are dyed in combination with propidium iodide (PI), can be by early apoptosis and evening
Phase apoptotic cell is distinguished.The sum of early apoptosis rate and late apoptic rate are total apoptosis rate.As shown in fig. 6,0.1,1,10 μM dense
MMQ Apoptosis can be effectively induced after degree allyl isothiocyanate processing 72h, as allyl isothiocyanate concentration increases
Add, the apoptosis rate of MMQ cells gradually rises, and is in apparent dose dependent.
Prolactin pituitary MMQ's is thin as it can be seen that allyl isothiocyanate can effectively inhibit for the result of complex chart 5 and Fig. 6
Born of the same parents are proliferated, and are in apparent time dependence and dose dependent.At the same time, allyl isothiocyanate can be induced significantly
MMQ apoptosis.
Embodiment 3
Under aseptic condition, collect in exponential phase, MMQ cells in good condition, physiological saline centrifuge washing is for several times
Serum is removed, and is diluted in physiological saline.Every nude mice by subcutaneous inoculation 1 × 107A cell/nude mice.It weighs within every two days naked
Mouse weight records the variation of weight.The every two days length and width with vernier caliper measurement tumour, with formula V=a2× b/2 calculates swollen
Knurl is accumulated, and wherein a is width, and b is length, unit：Centimetre.Tumor-bearing mice is randomly divided into 4 groups of (PBS solvents pair containing 0.1%DMSO
According to group, 25mg/kg allyl isothiocyanates group, 50mg/kg allyl isothiocyanates group, 100mg/kg allyl isothiocyanates
Group), every group 7, gastric infusion 4 weeks removes tumor size, weighs and record, the results are shown in Figure 7.
According to the result of Fig. 7 as it can be seen that allyl isothiocyanate can effectively inhibit prolactin pituitary MMQ transplanted tumor in nude mice
The growth of model is in apparent dose dependent.
The preferred embodiment of the disclosure is described in detail above in association with attached drawing, still, the disclosure is not limited to above-mentioned reality
The detail in mode is applied, in the range of the technology design of the disclosure, a variety of letters can be carried out to the technical solution of the disclosure
Monotropic type, these simple variants belong to the protection domain of the disclosure.
It is further to note that specific technical features described in the above specific embodiments, in not lance
In the case of shield, can be combined by any suitable means, in order to avoid unnecessary repetition, the disclosure to it is various can
The combination of energy no longer separately illustrates.
In addition, arbitrary combination can also be carried out between a variety of different embodiments of the disclosure, as long as it is without prejudice to originally
Disclosed thought equally should be considered as disclosure disclosure of that.
Claims (7)
1. purposes of the allyl isothiocyanate in the drug for preparing treatment functional pituitary adenoma.
2. purposes according to claim 1, wherein the functional pituitary adenoma is prolactin pituitary.
3. purposes according to claim 1 or 2, wherein the content of allyl isothiocyanate is 0.1- in the drug
200mg/g。
4. purposes according to claim 3, wherein the dosage form of the drug is oral agents.
5. purposes according to claim 4, wherein the oral agents are pill, tablet, powder or capsule.
6. purposes according to claim 1 or 2, wherein the dosage of allyl isothiocyanate is every kilogram of adult
Weight 1-100mg.
7. purposes according to claim 1, wherein shown in the structure of allyl isothiocyanate such as formula (1)；
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810476282.0A CN108478554B (en) | 2018-05-17 | 2018-05-17 | Application of allyl isothiocyanate in preparation of medicine for treating functional pituitary adenoma |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810476282.0A CN108478554B (en) | 2018-05-17 | 2018-05-17 | Application of allyl isothiocyanate in preparation of medicine for treating functional pituitary adenoma |
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| CN108478554A true CN108478554A (en) | 2018-09-04 |
| CN108478554B CN108478554B (en) | 2019-12-13 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111375063A (en) * | 2018-12-29 | 2020-07-07 | 北京市神经外科研究所 | Application of protein function inhibitor in preparation of medicine for treating functional pituitary adenoma |
| CN111568892A (en) * | 2020-05-26 | 2020-08-25 | 中南大学湘雅二医院 | Use of AITC |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103462935A (en) * | 2013-09-13 | 2013-12-25 | 上海海虹实业(集团)巢湖今辰药业有限公司 | Allyl isothiocyanate nano-lipid carrier |
-
2018
- 2018-05-17 CN CN201810476282.0A patent/CN108478554B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103462935A (en) * | 2013-09-13 | 2013-12-25 | 上海海虹实业(集团)巢湖今辰药业有限公司 | Allyl isothiocyanate nano-lipid carrier |
Non-Patent Citations (1)
| Title |
|---|
| YUESHENG ZHANG: "Allyl isothiocyanate as a cancer chemopreventive phytochemical", 《MOL NUTR FOOD RES》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111375063A (en) * | 2018-12-29 | 2020-07-07 | 北京市神经外科研究所 | Application of protein function inhibitor in preparation of medicine for treating functional pituitary adenoma |
| CN111375063B (en) * | 2018-12-29 | 2022-02-18 | 北京市神经外科研究所 | Application of protein function inhibitor in preparation of medicine for treating functional pituitary adenoma |
| CN111568892A (en) * | 2020-05-26 | 2020-08-25 | 中南大学湘雅二医院 | Use of AITC |
| WO2021237879A1 (en) * | 2020-05-26 | 2021-12-02 | 中南大学湘雅二医院 | Use of aitc |
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| CN108478554B (en) | 2019-12-13 |
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Granted publication date: 20191213 Termination date: 20200517 |