CN104958285A - Non-small cell lung cancer resistant medicinal composition and an application thereof - Google Patents
Non-small cell lung cancer resistant medicinal composition and an application thereof Download PDFInfo
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- CN104958285A CN104958285A CN201510315276.3A CN201510315276A CN104958285A CN 104958285 A CN104958285 A CN 104958285A CN 201510315276 A CN201510315276 A CN 201510315276A CN 104958285 A CN104958285 A CN 104958285A
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Abstract
The invention discloses a non-small cell lung cancer resistant medicinal composition and an application thereof. The medicinal composition is prepared from an active component and an auxiliary material, wherein the active component comprises 4-amino-3-methyl-2-naphthoic acid. A result of researches of the influences of 4-amino-3-methyl-2-naphthoic acid on the growth of human lung cancer A549 cell nude mouse transplantation tumors shows that 4-amino-3-methyl-2-naphthoic acid can substantially inhibit the growth of the transplantation tumors; and a result of researches about acute toxicity test shows that mice taking a large dosage of the medicinal composition do not die, and all systems and target organs do not have corresponding toxic response.
Description
Technical field
The invention belongs to medical art, in particular to a kind of pharmaceutical composition and application thereof of anti-nonsmall-cell lung cancer.
Background technology
Cancer is one of malignant disease of serious threat human health.Over nearly 30 years, China's cancer incidence is in the quick rising stage, and cancer morbidity is about 2,00/,100,000 people, and annual pathogenesis of cancer number about 2,600,000, is controlling more than patient 7,000,000 people, dead 1,800,000 people.At present, it is the fastest that pulmonary carcinoma is that M & M increases, to one of population health and the maximum malignant tumor of life threat.According to the difference of its biological property, pulmonary carcinoma can be divided into small cell lung cancer and nonsmall-cell lung cancer.Nonsmall-cell lung cancer (Not-small cell lung cancer, hereinafter referred to as NSCLC) accounts for more than 85% of pulmonary carcinoma, comprises scale cancer, adenocarcinoma and large cell carcinoma etc.Small cell lung cancer grade malignancy is the highest, aggressivity is strong, and metastasis early, often just has when making a definite diagnosis blood vessel to be invaded, therefore enters plateau for its treatment, and nonsmall-cell lung cancer is many keeps in position for a long time, and this is just conducive to clinical treatment and medication.But because lung cancer morbidity mechanism is unclear, lack effective early diagnosis and mean of defense, time medical, most of patients has lost surgical engine meeting, and only have 20% can be treated surgically, postoperative recurrence and the rate of transform are still up to more than 50%.So, the subject matter faced now be how to improve the effective percentage for the treatment of, extend life cycle, quality of making the life better.
CN103980139A discloses sunaptic acid compounds and preparation method thereof, this compound is 4-amino-3-methyl-2-naphthoic acid, preparation method is as follows: (1) for initiation material, with thionyl chloride and methanol by carboxylic esterification, obtains compound 2 with compound 13-hydroxy-2-naphthoic acid; (2) compound 2 nitric acid nitro on naphthalene nucleus 4, obtains compound 3; (3) compound 3 Trifluoromethanesulfonic anhydride substituted hydroxy makes compound 4; (4) compound 4 obtains compound 5 by Suzuki coupling; (5) nitroreduction is become amino by compound 5 palladium carbon, obtains compound 6; (6) Ester hydrolysis is obtained final product compound by compound 6 in the basic conditions.At present, this compound of bibliographical information is not still had to have the biological activity of anti-nonsmall-cell lung cancer.
Summary of the invention
The object of the present invention is to provide a kind of pharmaceutical composition of anti-nonsmall-cell lung cancer.This medicine for active component, can be used for the preparation of anti-nonsmall-cell lung cancer pharmaceutical preparation with 4-amino-3-methyl-2-naphthoic acid.
In order to realize object of the present invention, the impact test that inventor is grown typeⅡ pneumocyte transplanted tumor in nude mice by research 4-amino-3-methyl-2-naphthoic acid, found that 4-amino-3-methyl-2-naphthoic acid significantly can suppress the growth of transplanted tumor; Studied by acute toxicity test, after result shows heavy dose of administration there is not death in mice, and each system and target organ do not show corresponding toxic reaction.Based on above-mentioned result of the test, technical scheme provided by the invention is summarized as follows:
A pharmaceutical composition for anti-nonsmall-cell lung cancer, is prepared from by active component and pharmaceutically acceptable adjuvant, and described active component comprises 4-amino-3-methyl-2-naphthoic acid.Preferably, the pharmaceutical composition of anti-nonsmall-cell lung cancer described above, wherein said active component is made up of as sole component 4-amino-3-methyl-2-naphthoic acid.This compound 4-amino-3-methyl-2-naphthoic acid is pale solid, and its hydrogen nuclear magnetic resonance modal data is 1H-NMR (DMSO; 400HZ) 2.509 (s, 3H) 7.507 (m, 1H) 7.581 (t, 1H) 7.846 (s, 1H) 7.924 (d, 1H) 8.230 (d, 1H), its chemical structural formula is shown below:
The pharmaceutical composition of anti-nonsmall-cell lung cancer of the present invention can be oral formulations, comprises tablet, capsule, granule, drop pill, oral liquid.It should be noted that, according to the common process of formulation art, those skilled in the art is easy to acceptable adjuvant on 4-amino-3-methyl-2-naphthoic acid and pharmaceutics to be prepared into conventional oral formulations, as oral liquid, granule, tablet, capsule.Wherein, on pharmaceutics, acceptable adjuvant comprises filler, disintegrating agent, binding agent, correctives, lubricant etc.Described filler is selected from following one or more: pregelatinized Starch, lactose, mannitol and microcrystalline Cellulose; Described disintegrating agent is selected from following one or more: carboxymethyl starch sodium, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose and low-substituted hydroxypropyl cellulose; Described binding agent is selected from following one or more: starch slurry, hydroxypropyl cellulose solution, povidone solution; Described lubricant is selected from following one or both: magnesium stearate, Pulvis Talci.
In addition, the present invention also provides a kind of compound novelty teabag, that is: the application of 4-amino-3-methyl-2-naphthoic acid in the medicine of the anti-pulmonary carcinoma of preparation.Pulmonary carcinoma preferably described is further nonsmall-cell lung cancer.
Compared with prior art, the 4-amino-3-methyl-2-naphthoic acid that the present invention relates to, on the impact test of typeⅡ pneumocyte transplanted tumor in nude mice growth, found that 4-amino-3-methyl-2-naphthoic acid significantly can suppress the growth of transplanted tumor; Studied by acute toxicity test, result shows this medicine and does not show corresponding toxic reaction to each system such as respiratory system, motor function, convulsions tic reaction, eyelid indication, cardiovascular indications, salivation, perpendicular hair, the pain sensation, muscular tension, gastrointestinal indication, skin and target organ, explanation anticancer therapeutic is remarkable, toxic and side effects is little, can be developed into the new drug of anti-nonsmall-cell lung cancer.
Detailed description of the invention
Be below the in vitro tests process of this compound, technical scheme of the present invention is done to describing further, but protection scope of the present invention be not limited to this test example.Every do not deviate from the present invention's design change or equivalent substituting include within protection scope of the present invention.
The experimental study of the anti-human lung cancer A549 cell transplanted tumor in nude mice of embodiment 1:4-amino-3-methyl-2-naphthoic acid
SPF level BALB/c-nu mice 24,6 week age, weight l6g-18g.Take the logarithm trophophase lung cancer A549 cell, adjusting cell concentration with aseptic PBS is 3 × 10
7individual/mL, at BALB/c-nu mouse back subcutaneous vaccination 0.1ml, treats that subcutaneous transplantation tumor volume reaches 75mm
3during left and right (about 10d), be divided into 3 groups by tumor volume and mice with tumor body weight homeostatic principle: model control group, positive controls and test group, often organize 8.1d after grouping, positive controls gavage gefitinib 50.0mg/kg, test group gavage 4-amino-3-methyl-2-naphthoic acid 12.6mg/kg, model control group gavage gives isopyknic normal saline; Each group daily 1 time, amount to 10d, after last administration 48h dislocation put to death mice, excision transplanted tumor, take tumor weight.Tumour inhibiting rate (%) IR=(1-medicine group tumor weight-average value/model control group tumor weight-average value) × 100%.What weighed by tumor relatively observes the impact of medicine on the growth of typeⅡ pneumocyte nude mice suppression tumor.Result of the test shows (see table 1): compared with model control group, and each medication therapy groups all has significant difference (P < 0.05 or P < 0.01) to the inhibitory action that typeⅡ pneumocyte transplanted tumor in nude mice grows; In addition, compared with positive controls, the tumor-inhibiting action of test group is stronger, but the two compares not statistically significant (P > 0.05).
Table 1: each group transplanted tumor weighs and tumour inhibiting rate compares
| Group | Sample size | Tumor heavy (mg) | Tumour inhibiting rate (%) |
| Model control group | 8 | 512.27±72.49 | - |
| Positive controls | 8 | 294.04±83.71 ★ | 42.60 |
| Test group | 8 | 268.51±70.33 ★★ | 47.58 |
Compare with model control group,
★p < 0.05,
★ ★p < 0.01.
The acute toxicity test research of embodiment 2:4-amino-3-methyl-2-naphthoic acid
KM mice, 50, male and female half and half, body weight 18-20g, supply every day Beijing Australia of section pull together feed corporation,Ltd produce common Mus full-valence pellet feed, drinking water is pure water.Mice buys the rear laundering period through observing no abnormality seen reaction, and diet is normal.Adopt the method for distributing by body weight stratified random that mice is divided into matched group (placebo) and tested group (compound) by sex, often group 22, male and female half and half, random number, to make marks at mice different parts with picric acid and distinguish.Often organize No. 1-20 for formal test animal, No. 21-22 is animal for subsequent use, and test method is identical.The administration day before yesterday of mice fasting (can't help water) at dusk, give mouse stomach 2 times with 1.26g/kg, two minor tick 6h by 4-amino-3-methyl-2-naphthoic acid, the total gavage amount of mice is 2.52g/kg/d, is equivalent to about 200 times of clinical people's dosage.
Each system such as respiratory system, motor function, convulsions tic reaction, eyelid indication, cardiovascular indications, salivation, perpendicular hair, the pain sensation, muscular tension, gastrointestinal indication, skin and target organ are analyzed, determines tissue, organ and system that toxicity may relate to.At once start after administration, observe administration mice on the same day with or without above poisoning symptom.If there is not death, then continue to raise 14d, every 7d and take body weight 1 time.Taking off cervical vertebra during off-test and put to death mice, gross anatomy is carried out to major organs such as the heart, liver, spleen, lung, kidneys, when finding that organ occurs that volume, color, quality etc. change, then histopathological examination being carried out to the organ changed.
Compare with matched group, after heart-nourishing particle tested group of little raticide, 7d, 14d body weight is without obviously alleviating.Gross anatomy is carried out to test mice, has no the change that histoorgan has volume, color, quality.Give mice medicine of the present invention 2 times (namely total dosage is for 2.52g/kg/d) with maximum dosage-feeding, be equivalent to 200 times of clinical people's dosage.Under this dosage there is not death in mice, and each system and target organ do not show corresponding toxic reaction.It is abnormal that gross anatomy has no each organs and tissues.
Claims (5)
1. a pharmaceutical composition for anti-nonsmall-cell lung cancer, said composition is prepared from by active component and adjuvant, it is characterized in that: described active component comprises 4-amino-3-methyl-2-naphthoic acid.
2. the pharmaceutical composition of anti-nonsmall-cell lung cancer according to claim 1, is characterized in that: described active component is made up of as sole component 4-amino-3-methyl-2-naphthoic acid.
3. the pharmaceutical composition of anti-nonsmall-cell lung cancer according to claim 1, is characterized in that: it is oral formulations, comprises tablet, capsule, granule, drop pill and oral liquid.
The application of 4.4-amino-3-methyl-2-naphthoic acid in the medicine of the anti-pulmonary carcinoma of preparation.
5. the application of 4-amino-3-methyl-2-naphthoic acid in the medicine of the anti-pulmonary carcinoma of preparation according to claim 3, is characterized in that: described pulmonary carcinoma is nonsmall-cell lung cancer.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110272342A (en) * | 2019-07-16 | 2019-09-24 | 辽宁中医药大学 | A kind of naphthoic acid compound and its extraction separation method and purposes in purslane |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1675154A (en) * | 2002-06-07 | 2005-09-28 | 科蒂科股份有限公司 | Napththalene derivatives which inhibit the cytokine or biological activity of macrophage migration inhibitory factor (MIF) |
| CN103980139A (en) * | 2014-05-27 | 2014-08-13 | 天津市斯芬克司药物研发有限公司 | Naphthoic acid compound and preparation method thereof |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1675154A (en) * | 2002-06-07 | 2005-09-28 | 科蒂科股份有限公司 | Napththalene derivatives which inhibit the cytokine or biological activity of macrophage migration inhibitory factor (MIF) |
| CN103980139A (en) * | 2014-05-27 | 2014-08-13 | 天津市斯芬克司药物研发有限公司 | Naphthoic acid compound and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| OGECHI N. IKEDIOBI等: "In vitro differential sensitivity of melanomas to phenothiazines is based on the presence of codon 600 BRAF mutation", 《MOL CANCER THER》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110272342A (en) * | 2019-07-16 | 2019-09-24 | 辽宁中医药大学 | A kind of naphthoic acid compound and its extraction separation method and purposes in purslane |
| CN110272342B (en) * | 2019-07-16 | 2021-12-14 | 辽宁中医药大学 | Naphthoic acid compound in purslane and extraction and separation method and application thereof |
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