CN103860561B - A kind of pharmaceutical composition and application thereof preventing and treating breast carcinoma - Google Patents
A kind of pharmaceutical composition and application thereof preventing and treating breast carcinoma Download PDFInfo
- Publication number
- CN103860561B CN103860561B CN201410135416.4A CN201410135416A CN103860561B CN 103860561 B CN103860561 B CN 103860561B CN 201410135416 A CN201410135416 A CN 201410135416A CN 103860561 B CN103860561 B CN 103860561B
- Authority
- CN
- China
- Prior art keywords
- ftorafur
- pharmaceutical composition
- cetirizine hydrochloride
- breast carcinoma
- tumor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Abstract
The invention discloses a kind of pharmaceutical composition and the application thereof that prevent and treat breast carcinoma, the active component of this pharmaceutical composition comprises cetirizine hydrochloride and ftorafur, and in preferred active component, the weight ratio of cetirizine hydrochloride and ftorafur is 1: 1-5.The pharmaceutical composition antitumor activity preventing and treating breast carcinoma provided by the invention is remarkable, and toxic and side effects is little.
Description
Technical field
The invention belongs to medical art, in particular to a kind of cancer therapy drug, particularly relate to a kind of pharmaceutical composition and the application thereof that prevent and treat breast carcinoma.
Background technology
Breast carcinoma is that one has a strong impact on one of even life-threatening modal malignant tumor of women's physical and mental health, and be the modal nauseating tumor of global women, its therapeutic modality is that auxiliary surgical is with chemotherapy, radiotherapy.Chemotherapy treats one of conventional non-operative treatment of breast carcinoma, but it has serious side effects.Therefore, improve tumor cell is research focus to the Sensitivity and Specificity of chemotherapeutic always.
Ftorafur (Tegafur, FT, FT-207) is one of miazines anticarcinogen, and it is the prodrug of 5-fluorouracil (5-FU), has inhibitory action to most solid tumor.Competent biosynthesis of disturbing blocking dna, RHA and protein in vivo, thus produce its antitumaous effect.Proved by medical basic research and clinical observation, ftorafur toxic and side effects is less, and chemotherapeutic index is higher, on immunosuppressive action and also less on the impact about immune internal organs, is can continuous safe drugs clinically.This medicine belongs to one of oral anti-cancer medicine few in number, and through gastrointestinal absorption after oral, within 1-3 hour, blood level reaches summit.Last longer than intravenously administrable, therefore its good therapeutic effect can be played.Be mainly used in gastric cancer, colon and rectum carcinoma, etc. digestive tract cancer, also can be used for breast carcinoma, primary hepatocarcinoma, cancer of pancreas and pulmonary carcinoma.In addition, to prevent recurrence after operation, transfer have certain curative effect.The topmost untoward reaction of ftorafur is symptom of digestive tract and bone marrow depression, and gastral untoward reaction such as nausea,vomiting,diarrhea etc. can badly influence the compliance of cancer patient.
Cetirizine (CetirizineHydrochloride) is a kind of potent H1 receptor antagonist, pharmaceutically active is stronger, there are good antiallergic and antiinflammatory action, and there is higher bioavailability, can not only suppress on a large scale after administration urticaria and skin general red, inflammatory cell can also be suppressed to divide a word with a hyphen at the end of a line to anaphylaxis position simultaneously, thus suppress later stage anaphylaxis, be a medicine with dual anti-allergic effects.Cetirizine hydrochloride oral formulations (tablet, capsule etc.) is applicable to respiratory system, skin and ocular allergies disease, comprise perennially allergic disease, as anaphylaxis dermatosis, urticaria, allergic rhinitis, eye pruritus, eye conjunctivitis and asthma etc.Cetirizine hydrochloride oral formulations is also used for the treatment of all kinds department of dermatologry anaphylactic disease, as the treatment of chronic, artificial property, col, tardy pressure, solar lentigines urticaria and atopic dermatitis etc.
At present, also do not have bibliographical information cetirizine hydrochloride to can be used to anti-breast cancer, do not have bibliographical information that cetirizine hydrochloride and ftorafur use in conjunction are treated breast carcinoma yet.
Summary of the invention
The present inventor is surprised to find that when applying the anaphylactic disease of cetirizine hydrochloride treatment patient with breast cancer clinically, and cetirizine hydrochloride coordinates ftorafur to have comparatively significant therapeutical effect to patient with breast cancer.Confirm that heavy dose of cetirizine hydrochloride has certain antitumor activity really by internal and external test subsequently, have also demonstrated cetirizine hydrochloride associating ftorafur simultaneously and there is collaborative anti-breast cancer effect more significantly.Therefore, the object of the present invention is to provide a kind of pharmaceutical composition and the pharmaceutical applications of preventing and treating breast carcinoma.
The present inventor is studied by lot of experiments, finally obtains following technical scheme:
Prevent and treat a pharmaceutical composition for breast carcinoma, active component comprises cetirizine hydrochloride and ftorafur.
Preferably, prevent and treat the pharmaceutical composition of breast carcinoma as mentioned above, in active component, the weight ratio of cetirizine hydrochloride and ftorafur is 1: 1-5.
Further preferably, prevent and treat the pharmaceutical composition of breast carcinoma as mentioned above, in active component, the weight ratio of cetirizine hydrochloride and ftorafur is 1: 2.5.
Again further preferably, prevent and treat the pharmaceutical composition of breast carcinoma as mentioned above, it can be made into oral formulations; Described oral formulations preferred tablet and capsule.
Again further preferably, the above-mentioned pharmaceutical composition preventing and treating breast carcinoma, the effective dose that in wherein said tablet or capsule, per unit preparation contains cetirizine hydrochloride is 50mg, and the effective dose containing ftorafur is 100mg-250mg.
Test confirms: it is active that heavy dose of cetirizine hydrochloride has certain anti-breast cancer cancer, significantly can suppress the growth of human breast carcinoma MDA-MB-231 cell transplanted tumor in nude mice.Therefore, second object of the present invention is the pharmaceutical applications providing a kind of compound, i.e. the purposes of cetirizine hydrochloride in the medicine preparing anti-breast cancer.In addition, also find in test, the tumor-inhibiting action highly significant of ftorafur+cetirizine hydrochloride high dose group, compare model control group and single medicine group all has pole significant difference (P < 0.01), this imply that the cetirizine hydrochloride of high dose can promote the active anticancer of ftorafur, two kinds of drug combinations demonstrate obvious synergism.Therefore, the 3rd object of the present invention is the pharmaceutical applications providing a kind of compositions, namely comprises the purposes of active component in the medicine preparing anti-breast cancer of cetirizine hydrochloride and ftorafur.
Compared with prior art, the pharmaceutical composition antitumor activity preventing and treating breast carcinoma provided by the invention is remarkable, and toxic and side effects is little, has enriched prior art, for adding a kind of potential anti-breast cancer new drug clinically, there is social meaning and the economic implications of highly significant.
Detailed description of the invention
Now further describe implementation process of the present invention and effect test by following examples, embodiment is only for the object of illustration, do not limit the scope of the invention, the simultaneously apparent change made according to the present invention of those of ordinary skill in the art and modification are also contained within the scope of the invention.
Embodiment 1: the preparation of tablet
Preparation technology:
Ftorafur, cetirizine hydrochloride are crossed 120 mesh sieves, is dissolved in 60-80 DEG C of hot water with beta-schardinger dextrin-, keep more than 60min, cooling, beta-schardinger dextrin-filters after separating out, and dries, sieves; Mannitol, low-substituted hydroxypropyl cellulose, aspartame cross 100 mesh sieves, take by recipe quantity, mix homogeneously, and it is appropriate to add distilled water, and granulate, dry, granulate, adds recipe quantity Pulvis Talci, mixing, tabletting and get final product.
Embodiment 2: the preparation of tablet
Preparation technology:
Ftorafur, cetirizine hydrochloride are crossed 120 mesh sieves, fully be ground with beta-schardinger dextrin-, lactose, carboxymethyl starch sodium, Fructus Citri Limoniae essence cross 100 mesh sieves, take by recipe quantity, mix homogeneously, add distilled water appropriate, granulate, dry, granulate, add recipe quantity magnesium stearate, mixing, tabletting and get final product.
Embodiment 3: cetirizine hydrochloride and ftorafur coupling pair
SPF level BALB/c-nu mice 40,6 week age, body weight 18g-20g.To be in exponential phase, the MDA-MB-231 breast cancer cell culture in glassware base of degree of converging 80% ~ 90% is inhaled and is abandoned, with phosphate buffer wash cell 2-3 time, trypsin 0.25%) digestion, collecting cell, again with phosphate buffer washing, piping and druming mixing, counting; Concentration is adjusted, by every nude mice dorsal sc inoculating cell number 1.0 × 10 again with serum-free RPMI-1640
7/ 0.2mL pallium cell injection is in nude mice dorsal sc.After inoculation, 7d starts, the subcutaneous visible lesser tubercle of oncocyte inoculation position, about 5mm × 5mm size; To the 10th day, tumor was about 7mm × 7mm size.
Get into tumor nude mice 35, adopt Stochastic sum homeostatic principle to be divided into 7 groups, often organize 5.Each group of gastric infusion, its tested material and dosage are: 1. matched group, and pure water 0.6mL/ is only; 2. ftorafur group (100mg/kg); 3. cetirizine hydrochloride low dose group (5mg/kg); 4. cetirizine hydrochloride high dose group (20mg/kg); 5. ftorafur (100mg/kg)+cetirizine hydrochloride low dosage (5mg/kg) group; 6. ftorafur (50mg/kg)+cetirizine hydrochloride high dose (20mg/kg) group.Each group of equal administration 2 weeks, once a day.
After last administration, 48h puts to death nude mice, and get transplanted tumor and measure tumor size, method is: measure Y-axis (L) and × axle (W) length bottom subcutaneous transplantation tumor with vernier cursor respectively, calculate gross tumor volume by formula [V=0.52 × L × W].Tumor-like hyperplasia (%)=[1-(the average tumor weight of experimental group average tumor weight/matched group)] × 100%.Strip transplanted tumor, each tumor tissue cuts part and carries out routine pathology section, and HE dyes.Under mirror, visible cancerous tissue is separated into the cancer nests differed in size by interfibrillar substance, visible lumen of gland, glandular tube spline structure; Cancerous cell differs in size, rounded or oval; Core is large, and kernel is obvious, and visible pathologic mitosis picture, the micro-basophilic of endochylema is translucent.Each group of Xenografts in nude mice growing state is in table 1.
Table 1 respectively group mice-transplanted tumor tumor-like hyperplasia compares
Compare with matched group,
*p < 0.05,
*p < 0.01;
Compare with ftorafur group,
$p < 0.05,
$$p < 0.01;
Compare with cetirizine hydrochloride high dose,
$p < 0.05,
$ $p < 0.01.
Can be found out by the result of the test of table 1, outside demineralizing acid cetirizine low dose group, other each experimental group tumor volumes and tumor are heavily starkly lower than matched group (P < 0.05 or P < 0.01), cetirizine hydrochloride low dose group does not show antitumor activity, but cetirizine hydrochloride high dose group shows certain tumor-inhibiting action, the tumor-inhibiting action highly significant of especially ftorafur+cetirizine hydrochloride high dose group, compare matched group and single medicine group all has pole significant difference (P < 0.01), this imply that the cetirizine hydrochloride of high dose can promote the active anticancer of ftorafur, two kinds of drug combinations demonstrate obvious synergism.
In addition, observe find at experimental session, ftorafur high dose group mice engenders movable minimizing, lethargy, diarrhoea, leukocyte and centriole Leukopenia, the performance such as appetite and weight loss, but all the other each group nude mices have no obvious adverse reaction.This illustrates, the ftorafur of high dose has comparatively significantly toxic reaction to nude mice, and when reducing ftorafur consumption, the toxic and side effects that this chemotherapy is brought obtains effective control.
Claims (2)
1. prevent and treat the pharmaceutical composition of breast carcinoma for one kind, be prepared from by active component and pharmaceutically acceptable auxiliaries, it is characterized in that: described active component is made up of cetirizine hydrochloride and ftorafur, described pharmaceutical composition is tablet, capsule, the effective dose that in described tablet or capsule, per unit preparation contains cetirizine hydrochloride is 50mg, and the effective dose containing ftorafur is 100mg-250mg.
2. the pharmaceutical composition preventing and treating breast carcinoma according to claim 1, is characterized in that: in described active component, the weight ratio of cetirizine hydrochloride and ftorafur is 1: 2.5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410135416.4A CN103860561B (en) | 2014-04-08 | 2014-04-08 | A kind of pharmaceutical composition and application thereof preventing and treating breast carcinoma |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410135416.4A CN103860561B (en) | 2014-04-08 | 2014-04-08 | A kind of pharmaceutical composition and application thereof preventing and treating breast carcinoma |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103860561A CN103860561A (en) | 2014-06-18 |
| CN103860561B true CN103860561B (en) | 2015-11-18 |
Family
ID=50899949
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410135416.4A Expired - Fee Related CN103860561B (en) | 2014-04-08 | 2014-04-08 | A kind of pharmaceutical composition and application thereof preventing and treating breast carcinoma |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103860561B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101193622A (en) * | 2005-06-09 | 2008-06-04 | 比奥里波克斯公司 | Method and composition for treating inflammatory disorders |
| WO2009124755A1 (en) * | 2008-04-08 | 2009-10-15 | European Molecular Biology Laboratory (Embl) | Compounds with novel medical uses and method of identifying such compounds |
| CA2828877A1 (en) * | 2011-03-03 | 2012-09-07 | Vanderbilt University | 6-alkyl-n-(pyridin-2-yl)-4-aryloxypicolinamide analogs as mglur5 negative allosteric modulators and methods of making and using the same |
-
2014
- 2014-04-08 CN CN201410135416.4A patent/CN103860561B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101193622A (en) * | 2005-06-09 | 2008-06-04 | 比奥里波克斯公司 | Method and composition for treating inflammatory disorders |
| WO2009124755A1 (en) * | 2008-04-08 | 2009-10-15 | European Molecular Biology Laboratory (Embl) | Compounds with novel medical uses and method of identifying such compounds |
| CA2828877A1 (en) * | 2011-03-03 | 2012-09-07 | Vanderbilt University | 6-alkyl-n-(pyridin-2-yl)-4-aryloxypicolinamide analogs as mglur5 negative allosteric modulators and methods of making and using the same |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103860561A (en) | 2014-06-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2016062290A1 (en) | Uses of triamterene medicament in preparing pharmaceutical composition for treatment of cancer | |
| CN102302737B (en) | Traditional Chinese medicine composition for treating gastric cancer | |
| WO2019149156A1 (en) | Uses of pulsatilla chinensis extract in preparing drug for treating viral and/or bacterial diseases | |
| CN101612400A (en) | 1 application of receptor antagonist in antitumor of angiotensin | |
| CN107530309A (en) | Eutectic composition and its medicinal usage | |
| CN103179967B (en) | Antineoplastic pharmaceutical compositions | |
| CN109224071A (en) | Prevention containing Berberine hydrochloride and PD1- antibody and/or the combination drug for treating tumour | |
| WO2019214723A1 (en) | Application of chlorogenic acid and compositions thereof in preparation of drugs for treating squamous cell carcinoma | |
| CN102579425B (en) | Caulis Spatholobi extract, application thereof and new application of isoliquiritigenin | |
| CN101062041B (en) | Novel medical function of cucurbitacin | |
| CN102526731B (en) | Pharmaceutical composition containing arctigenin | |
| CN103860561B (en) | A kind of pharmaceutical composition and application thereof preventing and treating breast carcinoma | |
| CN104069194B (en) | A kind of Chinese medicine composition with antitumaous effect and its production and use | |
| CN104189782A (en) | Anti-tumor medicament composition | |
| CN102319260A (en) | The application of cisplatin combined itraconazole isomer in preparation treatment lung-cancer medicament | |
| CN102178676B (en) | Medicinal composite for treating brain glioma | |
| CN101549032B (en) | Drug composition with the effect of anti-lung cancer and application in preparing anti-lung cancer drug | |
| CN106924331A (en) | A kind of application of Aidi preparation in treatment neuroblast tumor medicine is prepared | |
| CN106890189A (en) | Application of the chonglou saponin in antineoplastic sensitizer is prepared | |
| CN105434432B (en) | N-Hydroxyphthalimide class compound application in preparation of anti-tumor drugs | |
| CN104434948A (en) | Anti-pancreatic-cancer medicine composition and application thereof | |
| WO2019037671A1 (en) | Medicine for combined use in cancer treatment | |
| CN102225067A (en) | Pharmaceutical composition for treating stomach cancer | |
| CN107582866A (en) | Dendrobium candidum and Amlodipine are preparing the application process in treating hypertension drug | |
| CN102579756B (en) | Pharmaceutical composition containing ningpo yam rhizome extract and harmane alkaloid, as well as harmane alkaloid type derivatives, and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20151118 Termination date: 20180408 |