CN105769884B - A kind of pharmaceutical composition for treating lung cancer - Google Patents
A kind of pharmaceutical composition for treating lung cancer Download PDFInfo
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- CN105769884B CN105769884B CN201610170589.9A CN201610170589A CN105769884B CN 105769884 B CN105769884 B CN 105769884B CN 201610170589 A CN201610170589 A CN 201610170589A CN 105769884 B CN105769884 B CN 105769884B
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- Prior art keywords
- endoxan
- lung cancer
- pharmaceutical composition
- pipering
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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
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4525—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to field of medicaments, more particularly to a kind of pharmaceutical composition for treating lung cancer.The active ingredient of the pharmaceutical composition is endoxan and long handle pipering, and the two weight ratio is (2~10):1.The pharmaceutical composition of the treatment lung cancer of the present invention is significantly higher than endoxan exclusive use to the therapeutic effect of lung cancer, and there is wherein long handle pipering significant Synergy and attenuation to act on to endoxan.
Description
Technical field
The invention belongs to field of medicaments, and in particular to a kind of pharmaceutical composition for treating lung cancer.
Background technology
Lung cancer is one of current most common malignant tumour in the whole world, and its incidence of disease and the death rate are equal in all kinds of cancers in China
Rank first, and growth trend is presented in its morbidity and mortality.Current study show that the bad habit such as smoking is to cause lung cancer
The main reason for.
The conventional lung cancer therapy medicine of clinic includes endoxan, ifosfamide, Tarceva, Gefitinib etc..Its
Cyclophosphamide（The entitled cyclophosphanide of English, No. CAS is 50-18-0）Belong to broad-spectrum anti-cancer drug, clinically
For malignant lymphoma, leukaemia, Huppert's disease, breast cancer, orchioncus, oophoroma, nasopharyngeal carcinoma, neuroblast
Knurl, rhabdomyoma, osteosarcoma etc., are respectively provided with certain curative effect, but the stronger hepatotoxicity of the medicine and bone marrow suppression, and are easily caused de-
Hair.
Long handle pipering（Sylvatine, No. CAS is 42438-80-2）It is a kind of life initially found in Bi roots of grass seeds
Alkaloids（Kumar S, Kamboj J, Suman, Sharma S. Overview for various aspects of the
health benefits of Piper longum linn. fruit. J Acupunct Meridian Stud. 2011;4
(2):134-40.）, the bioactivity research at present both at home and abroad on long handle pipering is less.
The content of the invention
For above-mentioned prior art, it is an object of the invention to provide a kind of pharmaceutical composition for treating lung cancer.
To realize above-mentioned purpose, the technical solution adopted by the present invention is：
A kind of pharmaceutical composition for treating lung cancer, by the raw material system of pharmaceutically acceptable auxiliary material and following weight ratio
Into：The parts by weight of endoxan 2~10, the parts by weight of long handle pipering 1.
As the optimal technical scheme of the present invention, the weight ratio of the raw material is：The parts by weight of endoxan 3, long handle
The parts by weight of pipering 1.
As another optimal technical scheme of the present invention, the weight ratio of the raw material is：The parts by weight of endoxan 5, long handle
The parts by weight of pipering 1.
As the another optimal technical scheme of the present invention, the weight ratio of the raw material is：The parts by weight of endoxan 6, long handle
The parts by weight of pipering 1.
As another optimal technical scheme of the present invention, the weight ratio of the raw material is：The parts by weight of endoxan 8, long handle
The parts by weight of pipering 1.
The method of administration of aforementioned pharmaceutical compositions is one kind in oral administration or intravenous injection administration, and preferably vein is noted
Penetrate administration.
Endoxan described in technical scheme, the entitled cyclophosphanide of English, No. CAS is 50-
18-0；Long handle pipering described in technical scheme, the entitled sylvatine of English, No. CAS is 42438-80-2.
This is known in those skilled in the art.
Pharmaceutically acceptable auxiliary material described in technical scheme, such as cosolvent, excipient, preservative, pH
Conditioning agent etc., reference can be made to Yao Jing is edited《Pharmaceutic adjuvant application guide》（China Medical Science Press's August in 2011 1 day the 1st
Version）；She Siji, Wei Le, Zheng Junmin are compiled《Pharmaceutic adjuvant handbook》（Chemical Industry Press publishes on January 1st, 2005）Deng reference
Books.Pharmaceutical composition is generally prepared into the preparation of particular dosage form to facilitate clinical administration with auxiliary material, can join on preparation technique
See that Zhang Jianhong is edited《Drug preparation technique》（People's Health Publisher publishes on January 1st, 2009）.
The present inventor has found in experimental study, when the amount ratio of long handle pipering and endoxan is 1:(2~
10) when, long handle pipering has significant synergies to the effect of anti-lung cancer of endoxan, and can reduce endoxan
Toxicity.
Embodiment
The present invention is further explained with reference to embodiment.It should be appreciated that following examples are only used for solving
The present invention is released, rather than is limited the scope of the invention.
Embodiment 1 treats combination of oral medication and its preparation of lung cancer
The prescription for treating the combination of oral medication of lung cancer see the table below：
Preparation method：
1）Take recipe quantity endoxan, long handle pipering to cross 80 mesh sieves, be well mixed, obtain raw material fine powder；
2）Recipe quantity microcrystalline cellulose, sodium carboxymethyl starch, PVP, magnesium stearate, superfine silica gel powder is taken to cross 200 mesh respectively
Sieve；
3）By step 1）Gained raw material fine powder first premixes with microcrystalline cellulose powder, then adds sodium carboxymethyl starch, gathers
Dimension ketone, magnesium stearate, superfine silica gel powder are well mixed, and tabletting produces endoxan/long handle pipering composite tablet.
Embodiment 2 treats intravenous (IV) drug composition and its preparation of lung cancer
The prescription for treating the intravenous (IV) drug composition of lung cancer see the table below：
Preparation method：
1）Take recipe quantity mannitol to be mixed with water for injection, add recipe quantity endoxan at 30 DEG C, long handle pipering stirs
Mix uniformly, obtain with liquid A；
2) prescription carbon content active is added to liquid A, stands 2h after stirring, liquid B must be matched somebody with somebody by filtering；
3）It is 5.7 to lemon acid for adjusting pH is added with liquid B, is sub-packed in cillin bottle, -40 DEG C of pre-freezes 3 hours, with 15 under 40Pa
DEG C/h speed is warming up to -10 DEG C, is then warming up to -5 DEG C with 2.5 DEG C/h of speed, is incubated 16 hours, it is incubated at 28 DEG C of 80Pa
Produce within 2 hours endoxan/long handle pipering compound freeze-dried powder used for intravenous injection.
Embodiment 3 treats the intravenous injection administration pharmacodynamic study of the pharmaceutical composition of lung cancer
C57BL/6 mouse, male, 6 ~ 8 week old, the g of body weight 18 ~ 24.Lewis lung cancer cell lines are purchased from China Medical Science
Institute's Shanghai Experimental Animal Center.
Growth period Lewis lung carcinoma cell of taking the logarithm intraperitoneal injection is inoculated in C57BL/6 mouse, after 8 days under aseptic condition
Gather mouse ascites, phosphate buffer（pH7.6）Tumor cell suspension is made after washing, adjusts cell concentration 2 × 106Individual knurl is thin
Born of the same parents/mL, it is subcutaneous to be only inoculated in the right armpit of mouse with 0.2mL/, takes tumor-bearing mice to be randomly divided into 10 groups after 14 days, every group 6, each group
Animal is administered and dosage（mg/kg）It see the table below：
Tail vein injection is administered after wherein endoxan or long handle pipering are dissolved in water for injection by group 1,2 respectively；Group 3-
Endoxan and long handle pipering are dissolved in tail vein injection after water for injection by 10 to be administered.Each group animal is to be administered daily 1 time,
Successive administration 14 days.Each group mouse tumor knurl footpath is determined after the same day and administration is administered within the 15th day, calculates tumour inhibiting rate.
15th and and the difference in the 1st day knurl footpath be Dx, the 15th day knurl footpath is Dy, then tumour inhibiting rate calculation formula is（1-Dx/Dy）
×100%。
As a result it is as follows：
P values are the comparative result of each group and group 1 in upper table.P ＜ 0.05 are considered as significant difference.P ＜ 0.01 are considered as difference pole
Significantly.
As seen from the above table, long handle pipering is without tumor-inhibiting action（Group 2）, when the amount ratio of long handle pipering and endoxan is
1:When (2~10)（Group 3- groups 8）, endoxan tumour inhibiting rate significantly raises, wherein 4 groups（The use of long handle pipering and endoxan
Amount is than being 1:3）, 5 groups（The amount ratio of long handle pipering and endoxan is 1:5）, 6 groups（Long handle pipering and endoxan
Amount ratio is 1:6）, 7 groups（The amount ratio of long handle pipering and endoxan is 1:8）Endoxan tumour inhibiting rate is significantly higher than other
Group.
When the amount ratio of long handle pipering and endoxan is less than 1:10（Group 9）Or higher than 1:2（Group 10）When, endoxan
Tumour inhibiting rate is without notable rise phenomenon.
Embodiment 4 treats the gastric infusion pharmacodynamic study of the pharmaceutical composition of lung cancer
C57BL/6 mouse, male, 6 ~ 8 week old, the g of body weight 18 ~ 24.Lewis lung cancer cell lines are purchased from China Medical Science
Institute's Shanghai Experimental Animal Center.
Growth period Lewis lung carcinoma cell of taking the logarithm intraperitoneal injection is inoculated in C57BL/6 mouse, after 8 days under aseptic condition
Gather mouse ascites, phosphate buffer（pH7.6）Tumor cell suspension is made after washing, adjusts cell concentration 2 × 106Individual knurl is thin
Born of the same parents/mL, it is subcutaneous to be only inoculated in the right armpit of mouse with 0.2mL/, takes tumor-bearing mice to be randomly divided into 8 groups after 14 days, every group 6, each group is moved
Thing is administered and dosage（mg/kg）It see the table below：
Wherein endoxan or long handle pipering are dissolved in gastric infusion after water for injection by group 1,2 respectively；3-10 is organized by ring
Phosphamide and long handle pipering are dissolved in gastric infusion after water for injection.Each group animal is successive administration 14 by daily single
My god.The 15th day measure each group mouse tumor knurl footpath after the same day and administration is administered, calculates tumour inhibiting rate, the 15th with and the 1st day knurl footpath it
Difference is Dx, and the 15th day knurl footpath is Dy, then tumour inhibiting rate calculation formula is（1-Dx/Dy）×100%.Experimental result is as follows：
P values are the comparative result of each group and group 1 in upper table.P ＜ 0.05 are considered as significant difference.P ＜ 0.01 are considered as difference pole
Significantly.
As seen from the above table, long handle pipering is without notable tumor-inhibiting action（Group 2）, when the dosage of long handle pipering and endoxan
Than for 1:When (2~10)（Group 3- groups 6）, endoxan tumour inhibiting rate significantly raises, wherein 4 groups（Long handle pipering and endoxan
Amount ratio be 1:3）, 5 groups（The amount ratio of long handle pipering and endoxan is 1:5）, 6 groups（Long handle pipering and ring phosphinylidyne
The amount ratio of amine is 1:6）Endoxan tumour inhibiting rate is significantly higher than other groups.
When the amount ratio of long handle pipering and endoxan is less than 1:10（Group 8）Or higher than 1:2（Group 7）When, endoxan
Tumour inhibiting rate is without notable rise phenomenon.
Embodiment 5 treats the safety research of the pharmaceutical composition of lung cancer
C57BL/6 mouse, male, 6 ~ 8 week old, the g of body weight 18 ~ 24.Mouse 250 is taken, is randomly divided into 5 groups, every group 50
Only, commercially available syklofosfamid ampoule is injected intraperitoneally respectively（Shanxi C ＆ Y Pharmaceutical Co., Ltd.）And the prescription 1 of embodiment 2, embodiment 2
Freeze-dried powder prepared by prescription 3, the prescription 5 of embodiment 2, the prescription 6 of embodiment 2, the laggard end of line intravenous injection of physiological saline solution, every group
Set 5 dosage（By endoxan Rapid Dose Calculation）, respectively 151.3 mg/kg, 177.9 mg/kg, 209.4 mg/kg,
246.4 mg/kg, 299.8 mg/kg, every group of each dosage are 10 animals.Give observation post administration each group animal interior injection in 1 week
Site erythema, oedema etc. stimulate phenomenon and death condition, and each group median lethal dose LD50 is calculated with Bliss methods.Each group animal is noted
Penetrate position and have no obvious stimulation phenomenon.Each group animal endoxan LD50 values are as follows（LD50 units are mg/kg）：
From the above results, long handle pipering is remarkably improved the lethal dose of endoxan, reduces its acute toxicity.
Claims (7)
1. a kind of pharmaceutical composition for treating lung cancer, it is characterised in that described pharmaceutical composition is by pharmaceutically acceptable auxiliary
The raw material of material and following weight ratio is made：The parts by weight of endoxan 2~10, the parts by weight of long handle pipering 1.
2. the pharmaceutical composition for the treatment of lung cancer according to claim 1, it is characterised in that the weight ratio of the raw material is：
The parts by weight of endoxan 3, the parts by weight of long handle pipering 1.
3. the pharmaceutical composition for the treatment of lung cancer according to claim 1, it is characterised in that the weight ratio of the raw material is：
The parts by weight of endoxan 5, the parts by weight of long handle pipering 1.
4. the pharmaceutical composition for the treatment of lung cancer according to claim 1, it is characterised in that the weight ratio of the raw material is：
The parts by weight of endoxan 6, the parts by weight of long handle pipering 1.
5. the pharmaceutical composition for the treatment of lung cancer according to claim 1, it is characterised in that the weight ratio of the raw material is：
The parts by weight of endoxan 8, the parts by weight of long handle pipering 1.
6. the pharmaceutical composition of the treatment lung cancer according to any one of claim 1 to 5, it is characterised in that the medicine group
The method of administration of compound is one kind in oral administration or intravenous injection administration.
7. the pharmaceutical composition for the treatment of lung cancer according to claim 6, it is characterised in that the administration of described pharmaceutical composition
Approach is administered for intravenous injection.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610170589.9A CN105769884B (en) | 2016-03-24 | 2016-03-24 | A kind of pharmaceutical composition for treating lung cancer |
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| CN201610170589.9A CN105769884B (en) | 2016-03-24 | 2016-03-24 | A kind of pharmaceutical composition for treating lung cancer |
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| CN105769884A CN105769884A (en) | 2016-07-20 |
| CN105769884B true CN105769884B (en) | 2018-04-03 |
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| CN105748449B (en) * | 2016-03-22 | 2017-11-24 | 冷昌俊 | A kind of pharmaceutical composition for treating oophoroma |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101554409A (en) * | 2008-04-10 | 2009-10-14 | 周亚伟 | Long pepper alkaloid and preparation method, preparation and application thereof |
| CN102133385A (en) * | 2011-03-02 | 2011-07-27 | 青岛大学 | Ginger and white pepper composition, preparation method thereof and application thereof to preparation of medicaments for attenuation and synergia in cancer radiochemotherapy |
| CN102247355A (en) * | 2008-11-25 | 2011-11-23 | 周亚伟 | Anti-tumor application of guineensine |
| CN103585546A (en) * | 2013-11-16 | 2014-02-19 | 崔新明 | Application of traditional Chinese medicine composition to preparation of drugs for treating diarrhea caused by cancer chemotherapy |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK2299999T3 (en) * | 2008-06-04 | 2017-09-25 | Baylor College Medicine | STAT3 INHIBITORS |
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- 2016-03-24 CN CN201610170589.9A patent/CN105769884B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101554409A (en) * | 2008-04-10 | 2009-10-14 | 周亚伟 | Long pepper alkaloid and preparation method, preparation and application thereof |
| CN102247355A (en) * | 2008-11-25 | 2011-11-23 | 周亚伟 | Anti-tumor application of guineensine |
| CN102133385A (en) * | 2011-03-02 | 2011-07-27 | 青岛大学 | Ginger and white pepper composition, preparation method thereof and application thereof to preparation of medicaments for attenuation and synergia in cancer radiochemotherapy |
| CN103585546A (en) * | 2013-11-16 | 2014-02-19 | 崔新明 | Application of traditional Chinese medicine composition to preparation of drugs for treating diarrhea caused by cancer chemotherapy |
Non-Patent Citations (1)
| Title |
|---|
| 蝙蝠葛碱和胡椒碱对两株鼻咽癌细胞增殖的影响;丁航等;《广东医学院学报》;20030228;第21卷(第01期);16-17 * |
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