CN101467996B - Use of deuteroporphyrin derivates - Google Patents
Use of deuteroporphyrin derivates Download PDFInfo
- Publication number
- CN101467996B CN101467996B CN2007101732473A CN200710173247A CN101467996B CN 101467996 B CN101467996 B CN 101467996B CN 2007101732473 A CN2007101732473 A CN 2007101732473A CN 200710173247 A CN200710173247 A CN 200710173247A CN 101467996 B CN101467996 B CN 101467996B
- Authority
- CN
- China
- Prior art keywords
- deuteroporphyrin
- adenocarcinoma
- vinyl
- effect
- methoxy ethyl
- 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.)
- Active
Links
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of medicament and specifically relates to use of a deuteroporphyrin derivative. The invention provides use of deuteroporphyrin derivative in preparing medicament for treating squamous carcinoma or adenocarcinoma. The treatment with the deuteroporphyrin derivative or composition and medicament thereof to squamous carcinoma or adenocarcinoma has obvious growth-inhibiting effect and good dose effect relationship. A group with high dosage has strong and stable effect and stronger inhibiting effect than the positive control medicament, hemoporphyrin. The deuteroporphyrin derivative has no growth-inhibiting effect on tumour cells under a condition of non-laser radiation, no damaging effect on normal histiocytes with light or without light and little side effect.
Description
Technical field
The present invention relates to medical technical field, be specifically related to the purposes of deuteroporphyrin derivates.
Background technology
Squamous cell carcinoma (squamous cell carcinoma) is called for short scale cancer, often occurs in the position that the original squamous epithelial cancer of health covers, and locates like skin, oral cavity, lip, cervix uteri, vagina, esophagus, larynx etc.Some position such as bronchus, gallbladder, renal pelvis etc. are located, and cover though just often can't help squamous epithelial cancer, can squamous cell carcinoma take place through squamous metaplasia.Often be cauliflower form on these cancer naked eyes, also can form ulcer because of the cancerous tissue necrosis comes off.Cancerous tissue is also done infiltrative growth to deep layer simultaneously.
Adenoma (adenoma) is the tumor that is taken place by glandular epithelium, is more common in thyroid, ovary, mammary gland, salivary gland and intestinal etc. and locates.The adenoma of mucous glands is polypoid more, and the adenoma in the glandular organ then more is nodositas, and peplos is often arranged, clear with the normal surrounding tissue boundary.According to the constituent or the form characteristics of adenoma, can it be divided into types such as cystadenoma, fibroadenoma, pleomorphic adenoma and polypoid adenoma again.
Photodynamic therapy progressively becomes one of base therapy means of tumor.Photodynamic therapy is controlled the principle of cancer: can a kind of material that is photosensitizer of specificity picked-up mainly due to cancerous cell.Photosensitizer can rest in the cancerous cell after being absorbed by cancerous cell the long period.The avirulence of photosensitizer own, but after a kind of light (laser of 630nm commonly used) irradiation of special wavelength, can react with oxygen, produce a kind of activated state oxonium ion with toxic action, thus destruction of cancer cells.
The light power curing cancer drug hematoporphyrin derivative (hematoporphyrinderivative of domestic and international clinical use at present; HpD) and phytochrome II or the non-nurse sodium of porphin (Photofrin II or Sodium Pofimer) be and form indefinite mixing porphyrin preparation; Its tumor photo bio active component is indeterminate; And contain in a large number in vivo uniform distribution and remove the porphyrin of high light sensitization slowly, like hemoporphyrin, ethoxy vinyl deuteroporphyrin, protoporphyrin etc.The photosensitizer that with HpD is representative belongs to first generation photosensitizer; Their component is complicated; The effect of various compositions in the damage of light power do not understood fully so far yet; Account for the non-active ingredient of medicine total amount more than 20～80% and not only can not produce effective light power damaging action, become the chief culprit who causes normal structure generation photosensitivity reaction on the contrary the target tissue of pathological changes.Therefore, the stability of the tissue selectivity of first generation photosensitizer and light power damage strength is all very poor, and causes the skin photo sensitive reaction easily, and the lucifuge time is long.In addition, the absorption spectrum that mixes Porphyrin-Based Sensitizer the absorption band of red light portion very a little less than, absorptive red light well, the treatment degree of depth is not enough, also influences its clinical efficacy.
Summary of the invention
Technical problem to be solved by this invention is the problem to scale cancer or adenocarcinoma clinical treatment, develops the purposes of new deuteroporphyrin derivates in preparation treatment scale cancer or adenocarcinoma medicine.
Deuteroporphyrin derivates according to the invention (DpD) is for having the chemical compound of structure general formula (I):
Wherein, R1 and R2 independently are selected from 1-methoxy ethyl, 1-hydroxyethyl, vinyl respectively, and R1 and R2 can not be 1-hydroxyethyl or vinyl simultaneously,
Or their pharmaceutically acceptable salt.
In an embodiment, R1 and R2 are selected from 1-methoxy ethyl or 1-hydroxyethyl respectively, and R1 and R2 are inequality.
In a preferred embodiment, in order to solve the cost problem that purification brings, deuteroporphyrin derivates according to the invention also can be the compositions of being made up of following four kinds of porphyrins (hereinafter to be referred as how fragrant for pool):
(II) 3-(1-methoxy ethyl)-8-(1-hydroxyl second (III) 3,8-two (1-methoxy ethyl)
Base) deuteroporphyrin IX or 3-(1-hydroxyethyl)-8 deuteroporphyrin IX
-(1-methoxy ethyl) deuteroporphyrin IX
(IX) 3-(1-hydroxyethyl)-8-vinyl 3-(1-methoxy ethyl)-8-vinyl time (V))
Porphyrin IX or 3-vinyl-8-(1-methoxyl group porphyrin IX or 3-vinyl-8-(1-hydroxyl second
Ethyl) deuteroporphyrin IX. deuteroporphyrin IX yl)
The weight ratio of above-mentioned four kinds of porphyrins is:
(II) 3-(1-methoxy ethyl)-8-(1-hydroxyethyl) deuteroporphyrin IX
Or 3-(1-hydroxyethyl)-8-(1-methoxy ethyl) deuteroporphyrin IX 55 ± 5%
(III) 3,8-two (1-methoxy ethyl) deuteroporphyrin IX 20 ± 3%
(IV) 3-(1-methoxy ethyl)-8-vinyl deuteroporphyrin IX
Or 3-vinyl-8-(1-methoxy ethyl) deuteroporphyrin IX 15 ± 2%
(V)) 3-(1-hydroxyethyl)-8-vinyl deuteroporphyrin IX
Or 3-vinyl-8-(1-hydroxyethyl) deuteroporphyrin IX. 10 ± 2%
Wherein, " IX " is that Fischer is with a kind of mode of Roman number as the name of isomer type; " inferior leaf beautiful jade IX " 5 Fructus Citri tangerinae structure as follows (H.Fischer and H.orth " Die Chemie des Pyrr0ls "; ^kademische Verlagsgesellschaft, Leipzig Vol 1 and 111 (1934 and 1937).
One of in the preferred oral squamous cell carcinomas of scale cancer of the present invention, epithelium of cervix uteri scale cancer, the esophageal carcinoma or the bladder cancer.
One of in the preferred adenocarcinoma of stomach of adenocarcinoma of the present invention, the adenocarcinoma of colon.
Deuteroporphyrin derivates of the present invention or compositions (how fragrant for pool) can be by the said method preparations of Chinese patent CN1130364.
On the other hand, the present invention also provides a kind of pharmaceutical preparation of treating scale cancer or adenocarcinoma, comprises deuteroporphyrin derivates active substance of the present invention and pharmaceutical acceptable carrier.
When pharmaceutical preparation of the present invention during to the human body administration, daily dose is usually by prescriber's decision, and dosage generally becomes with age, body weight, sex and the reaction of individual patient and the order of severity of patient's symptom.Usually, adult's dosage is 1-500mg active component/kg body weight every day, is preferably 5-300mg active component/kg body weight every day, preferred especially 10-200mg active component/kg body weight every day.
Comprehensive embodiment; Deuteroporphyrin derivates of the present invention or compositions and pharmaceutical preparation treatment thereof have the obvious growth inhibitory action to scale cancer or adenocarcinoma; And being good dose-effect relationship, the high dose group effect is strong and stable, and its inhibitory action obviously is better than the positive control drug hemoporphyrin; The next growth unrestraint effect of non-laser irradiation condition to tumor cell.Under illumination and non-illumination condition, normal tissue cell is not all had lethal effect, side effect is little.
Description of drawings
How Fig. 1 is for the fragrant optical dynamic therapy effect to people's scale cancer Nude Mice KB of pool.
How Fig. 2 is for the fragrant optical dynamic therapy effect to people's adenocarcinoma of stomach Nude Mice MKN-28 of pool.
How Fig. 3 is for the fragrant optical dynamic therapy effect to human colon adenocarcinoma's Nude Mice HCT-116 of pool.
Specific embodiment
Below in conjunction with specific embodiment, further illustrate the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in the restriction scope of the present invention.The experimental technique of unreceipted actual conditions in the following example, usually according to normal condition, or the condition of advising according to manufacturer.Ratio and percentage ratio are based on weight, unless stated otherwise.
Embodiment more than 1 is for the growth inhibited effect of the fragrant external photodynamic effect of pool to human tumor cell line.
Many for mooring the fragrant Chinese patent CN1130364 preparation of pressing, compound method: the injection normal saline is diluted to desired concn, joins existing usefulness at present.
Positive control drug: (Beijing Pharmaceutical Ind. Inst., lot number: 981202) compound method: the injection normal saline is diluted to desired concn to Hematoporphyrine Injection, joins existing usefulness at present.
Light source: IEAu-3 type gold vapor laser, optical maser wavelength 627.8nm, electron institute, Chinese Academy of Sciences Beijing produces.Tumor cell line:
The strain of table 1 test personnel selection solid tumor cell
| Cell strain | The source | Histology source and type |
| KB HCT-116 MKN-45 HELA Eca-109 T-24 | ATCC NCI JFCR ATCC SIMM ATCC | Oral squamous cell carcinomas Squamous Carcinoma adenocarcinoma of colon Colon Adenocarcinoma adenocarcinoma of stomach Gastric Adenocarcinoma epithelium of cervix uteri scale cancer Cervical Squamous Carcinoma esophageal carcinoma Esophageal Carcinoma bladder cancer Bladder Carcinoma |
| The normal control cell | ||
| NIH-3T3 | ATCC | The mice embryonic fibroblast |
* abbreviation: ATCC:American Type Culture Collection
NCI：National?Cancer?Institute，USA
SIMM：Shanghai?Institute?of?Material?Medica，Chinese?Academy?of?Sciences
JFCR：Japan?Foundation?for?Cancer?Research
(Sulforhodamine B, SRB) detection of drugs is to the inhibitory action of tumor cell proliferation growth to use white staining of sulphonyl rhodamine B dawn.Key step is following:
According to the cell growth rate (doubling time) that trial test is measured, the exponential phase cell (table 2) of inoculation some is in 96 well culture plates (90 l/ hole).Adherent growth 24 hours adds the many for pool sweet smell or hemoporphyrin (10 l/ hole) of 5 variable concentrations under the lucifuge condition, each concentration is established three multiple holes; After dosing was hatched 3 hours, the rayed group adopted the gold vapor laser irradiation of 627.8nm wavelength, laser power density 20mw/cm
2, irradiation time is 5 minutes; Establish the contrast of normal saline solvent and the acellular zeroing hole of respective concentration simultaneously.Tumor cell is at 37 ℃, 5%CO then
2Cultivated again under the condition 72 hours, and discarded culture fluid, with 10% cold TCA fixed cell.Place after 1 hour with distilled water wash 5 times natural drying in the air for 4 ℃.Add SRB (Sigma) the 4mg/ml solution 100 l/ holes by the preparation of 1% glacial acetic acid then, dyeing is 15 minutes in the room temperature, removes supernatant, with 1% acetic acid washing 5 times, air drying.The Tris solution that adds 150 l/ holes at last, ELIASA (VERSAmax) 520nm wavelength are measured the OD value down, calculate inhibitory rate of cell growth with formula:
Suppression ratio=(OD value
Control wells-OD value
Dosing holes)/OD value
Control wells* 100%
According to each concentration suppression ratio, adopt LOGIT method calculation of half inhibitory concentration IC
50More than each experiment repetition 2-6 time, obtain the average IC that tests for 2-6 time
50Value is as the final index of the ability of inhibition.
With the positive contrast of photosensitizer hemoporphyrin, with the non-laser irradiation group that adds each medicine respective concentration as negative control.Establish the non-dosing group of above-mentioned 7 strain cells simultaneously and carry out the laser irradiation of same intensity.
The result:
How to see table 2 for details for mooring sweet smell and positive control drug hemoporphyrin cell in vitro toxic action to 6 strain human tumor cells and 1 strain normal tissue cell.
Table 2 is many for mooring sweet smell and the positive control drug hemoporphyrin external pharmacodynamic result to various human tumor cell lines
| Cell strain | IC 50(μM)±SD | |||
| How fragrant for pool | Hemoporphyrin | |||
| Illumination | Non-illumination | Illumination | Non-illumination | |
| KB HCT-116 MKN-45 HeLa Eca-109 T-24 NIH-3T3 | 0.15±0.07 0.16±0.07 0.20±0.07 0.14±0.49 0.18±0.00 0.18±0.21 ＞100 | ＞100 ＞100 ＞100 ＞100 ＞100 ＞100 ＞100 | 23.7±0.55 43.0±1.71 42.7±1.18 21.0±0.92 28.0±0.28 34.5±0.35 ＞100 | ＞100 ＞100 ＞100 ＞100 ＞100 ＞100 ＞100 |
The result shows that the pools that replace fragrant under laser irradiation condition more, and 6 strain human solid tumor cells such as KB, HeLa, T-24 are had very strong direct killing effect, IC
50Between 0.14-0.20 μ M, average IC
50Be 0.17 μ M, this effect does not have obvious selectivity to the growth inhibited effect of the solid tumor cell strain of different tissue sources.The positive control drug hemoporphyrin is under illumination condition, to the IC of above-mentioned 6 strain human solid tumor cells
50Between 21.0-43.0 μ M, average IC
50Be 32.3 μ M.Therefore, the pool sweet smell that replace demonstrate stronger killing tumor cell effect external than positive control drug hemoporphyrin more.Many for pool fragrant and hemoporphyrin two by reagent when not having laser irradiation, 6 strain human solid tumor cells are not all had growth inhibited effect, IC
50All greater than 100 μ M; In addition, simple laser irradiation does not show tangible lethal effect to tumor cell yet.To normal mouse tissue cell NIH-3T3, many all do not have lethal effect for pool sweet smell and positive control drug hemoporphyrin under illumination condition and non-illumination condition.
Many all have significant growth inhibited effect for the solid tumor cell strain to different tissue sources under laser irradiation condition of pool sweet smell, and its inhibitory action obviously is better than the positive control drug hemoporphyrin; The next growth unrestraint effect of non-laser irradiation condition to tumor cell.Many all do not have lethal effect to normal tissue cell for pool is fragrant under illumination and non-illumination condition.
Embodiment more than 2 is for the fragrant optical dynamic therapy effect to people's scale cancer KB, people's adenocarcinoma of stomach MKN-28, human colon adenocarcinoma HCT-116 Nude Mice of pool.
Many for mooring the fragrant Chinese patent CN1130364 preparation of pressing, compound method: the injection normal saline is diluted to desired concn, joins existing usefulness at present.
Positive control drug: (Beijing Pharmaceutical Ind. Inst., lot number: 981202) compound method: the injection normal saline is diluted to desired concn to Hematoporphyrine Injection, joins existing usefulness at present.
The BALB/cA nude mouse is provided by Shanghai Pharmaceutical Inst., Chinese Academy of Sciences.Age in days: 35-40 days, body weight: 18-22g, sex: the male and female dual-purpose is same sex with a collection of test.Every treated animal number: 12 of negative control group, 6 of administration groups.
The GGH-9708 optic dynamic tumor therapeutical apparatus, wavelength: 632.8nm.Zhejiang state light medical apparatus and instruments company limited is produced.The LM-99B laser power meter, China National Measuring Science Research Inst. produces.
According to the trial test result, how to be made as 2.5mg/kg, 5mg/kg, the low middle Senior Three dose groups of 10mg/kg for the fragrant dosage of pool; The dosage of positive control drug hemoporphyrin is 5mg/kg.Other establishes the negative matched group of injecting normal saline; The simple laser irradiation of not administration is the blank group.According to the trial test result, the treatment power density is 120mW/cm2, and irradiation time is 30 minutes.All detect output before and after each laser irradiation, guarantee that its fluctuation range is less than ± 5% with laser power meter.
Scale cancer KB, people's adenocarcinoma of stomach MKN-28, human colon adenocarcinoma HCT-116 Nude Mice, subcutaneous and set up by KB, MKN-28, HCT-116 tumor cell inoculation in nude mouse.The cell inoculation amount is respectively 6 * 10
6, 2 * 10
6, 4 * 10
6, inoculation is used after forming and in the nude mouse body, passing for 3 generations again after the transplanted tumor.
Experimental technique:
The tumor tissue of getting the growth animated period cuts into 1.5mm
3About, under aseptic condition, it is subcutaneous to be inoculated in the nude mouse back.Nude Mice treats that with vernier caliper measurement transplanted tumor diameter tumor growth is to 100-300mm
3After with the animal random packet.Use the method for measuring the tumor footpath, dynamic observe by examination thing antineoplastic effect.The measurement number of times of diameter of tumor is 2 times weekly.The hemoporphyrin group was carried out the irradiation treatment in 24 hours after an intravenous injection, the many group in an intravenous injection for the pool sweet smell carried out the irradiation treatment after 1 hour.The employing wavelength is that the laser of 632.8nm shines tumor, and laser power density is 120mW/cm
2, irradiation time is 30 minutes.The blank group is the simple irradiation group of not administration.Negative control group is given the equivalent normal saline simultaneously.Administration is disconnected neck execution nude mouse after 24 hours, and weighs.Gross tumor volume (tumor volume, computing formula TV) is:
TV＝1/2×a×b2
Wherein a, b represent length and width respectively.(relative tumorvolume, RTV), computing formula is: RTV=V to calculate relative tumour volume according to the result who measures
t/ V
0V wherein
0(d0) measures gained gross tumor volume, V during for minute cage administration
tGross tumor volume when measuring each time.The evaluation index of anti-tumor activity is relative tumor proliferation rate T/C (%), and computing formula is following:
T
RTV: treatment group RTV; C
RTV: negative control group RTV.
T/C (%) is less than 60, and it is effective to be regarded as experimental therapy through statistical procedures P value less than 0.05.
Result and discussion:
How red and swollen for transplanted tumor surface skin appearance in 2-6 hour behind pool sweet smell and the hemoporphyrin intravenous injection optical dynamic therapy, skin darkening is moist after 12-24 hour, and skin is black drying after 7 days, and the surperficial crust of part transplanted tumor can come off in about about 14 days.
How to see Fig. 1-6 for mooring the optical dynamic therapy result of fragrant intravenous injection optical dynamic therapy to people's scale cancer KB, people's adenocarcinoma of stomach MKN-28, human colon adenocarcinoma HCT-116 Nude Mice.Experimental result shows, and is many for the fragrant intravenously administrable 2.5mg/kg optical dynamic therapy groups of pool when off-test, is 38.8-81.7 to the T/C (%) of people's scale cancer KB; 5mg/kg optical dynamic therapy group, T/C (%) is 30.6-50.5; 10mg/kg optical dynamic therapy group, T/C (%) is 13.8-30.6.Many during off-test for the fragrant intravenously administrable 2.5mg/kg optical dynamic therapy groups of pool, be 95.3-132.5 to the T/C (%) of people's adenocarcinoma of stomach MKN-28; 5mg/kg optical dynamic therapy group, T/C (%) is 50.4-115.8; 10mg/kg optical dynamic therapy group, T/C (%) is 7.2-11.7.Many during off-test for the fragrant intravenously administrable 2.5mg/kg optical dynamic therapy groups of pool, be 52.6-112.0 to the T/C (%) of human colon adenocarcinoma HCT-116; 5mg/kg optical dynamic therapy group, T/C (%) is 35.9-56.3; 10mg/kg optical dynamic therapy group, T/C (%) is 14.2-26.1.The result shows that the fragrant optical dynamic therapies of pool that replace all have the obvious growth inhibitory action to 3 kinds of people's cancer Nude Mice more, and is good dose-effect relationship, and the high dose group effect is strong and stable.Simple laser irradiation does not all have the growth inhibited effect to above-mentioned three kinds of Nude Mice.Hemoporphyrin intravenous injection optical dynamic therapy all has certain growth inhibited effect to 3 kinds of people's cancer nude mouse models, but test stability is not fine.The no animal dead of each group does not have the overt toxicity reaction yet in the process of the test.
Conclusion:
Many all have significant growth inhibited effect for the fragrant intravenously administrable 10mg/kg optical dynamic therapies of pool to people's scale cancer KB, people's adenocarcinoma of stomach MKN-28, human colon adenocarcinoma HCT-116 Nude Mice, and inhibitory action is stronger and stablize than positive control drug hemoporphyrin.
Scope of the present invention does not receive the restriction of said specific embodiments, and said embodiment is only desired also to comprise the method and the component of functional equivalent in the scope of the invention as the single example of illustrating various aspects of the present invention.In fact, except content as herein described, those skilled in the art can easily grasp multiple improvement of the present invention with reference to the description and the accompanying drawing of preceding text.Said improvement also falls within the scope of appended claims.
Claims (1)
1. the purposes of deuteroporphyrin derivates in preparation optical dynamic therapy scale cancer or adenocarcinoma medicine is characterized in that said deuteroporphyrin derivates is for by following four kinds of compositionss that porphyrin is formed:
(II) 3-(1-methoxy ethyl)-8-(1-hydroxyl second
Base) deuteroporphyrin IX or 3-(1-hydroxyl second (III) 3,8-two (1-methoxy ethyl)
Base)-8-(1-methoxy ethyl) deuteroporphyrin IX deuteroporphyrin IX
(IV) 3-(1-hydroxyethyl)-8-vinyl 3-(1-methoxy ethyl)-8-vinyl time (V))
Porphyrin IX or 3-vinyl-8-(1-methoxyl group porphyrin IX or 3-vinyl-8-(1-hydroxyl second
Ethyl) deuteroporphyrin IX deuteroporphyrin IX yl)
The weight ratio of above-mentioned four kinds of porphyrins is:
(II) 3-(1-methoxy ethyl)-8-(1-hydroxyethyl) deuteroporphyrin IX
Or 3-(1-hydroxyethyl)-8-(1-methoxy ethyl) deuteroporphyrin IX 55 scholars 5%
(III) 3,8-two (1-methoxy ethyl) deuteroporphyrin IX 20 scholars 3%
(IV) 3-(1-methoxy ethyl)-8-vinyl deuteroporphyrin IX
Or 3-vinyl-8-(1-methoxy ethyl) deuteroporphyrin IX 15 scholars 2%
(V)) 3-(1-hydroxyethyl)-8-vinyl deuteroporphyrin IX
Or 3-vinyl-8-(1-hydroxyethyl) deuteroporphyrin IX 10 scholars 2%,
Said scale cancer one of is selected from oral squamous cell carcinomas, epithelium of cervix uteri scale cancer, the esophageal carcinoma or the bladder cancer, and said adenocarcinoma is adenocarcinoma of stomach or adenocarcinoma of colon.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007101732473A CN101467996B (en) | 2007-12-27 | 2007-12-27 | Use of deuteroporphyrin derivates |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007101732473A CN101467996B (en) | 2007-12-27 | 2007-12-27 | Use of deuteroporphyrin derivates |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101467996A CN101467996A (en) | 2009-07-01 |
| CN101467996B true CN101467996B (en) | 2012-05-09 |
Family
ID=40825958
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2007101732473A Active CN101467996B (en) | 2007-12-27 | 2007-12-27 | Use of deuteroporphyrin derivates |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101467996B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106795169B (en) * | 2014-08-27 | 2019-08-13 | 彩虹医药高科技有限公司 | Light hexyl ether compound and its pharmaceutical composition and purposes |
| CN112707911A (en) * | 2020-12-25 | 2021-04-27 | 范平生 | Preparation method and application of hematoporphyrin/verapamil conjugate |
| CN112645959A (en) * | 2020-12-25 | 2021-04-13 | 范平生 | Nitric ester NO donor type hematoporphyrin derivative and preparation method and application thereof |
| CN112608325A (en) * | 2020-12-25 | 2021-04-06 | 范平生 | Preparation and application of hematoporphyrin derivative of hematoporphyrin and verapamil fragment |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1312251A (en) * | 2001-01-11 | 2001-09-12 | 上海复旦张江生物医药股份有限公司 | Preparation of partially synthesized deuteroporphyrin derivative and its freeze dried injection |
| CN1130364C (en) * | 2000-02-28 | 2003-12-10 | 上海复旦张江生物医药股份有限公司 | Deuteroporphyvin derivative, its preparing method and freeze dried preparation for injection |
| CN1786001A (en) * | 2005-12-20 | 2006-06-14 | 重庆市华鼎现代生物制药有限责任公司 | Composition stable blood porphrin derivative, its preparation method and injection agent |
-
2007
- 2007-12-27 CN CN2007101732473A patent/CN101467996B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1130364C (en) * | 2000-02-28 | 2003-12-10 | 上海复旦张江生物医药股份有限公司 | Deuteroporphyvin derivative, its preparing method and freeze dried preparation for injection |
| CN1312251A (en) * | 2001-01-11 | 2001-09-12 | 上海复旦张江生物医药股份有限公司 | Preparation of partially synthesized deuteroporphyrin derivative and its freeze dried injection |
| CN1786001A (en) * | 2005-12-20 | 2006-06-14 | 重庆市华鼎现代生物制药有限责任公司 | Composition stable blood porphrin derivative, its preparation method and injection agent |
Non-Patent Citations (3)
| Title |
|---|
| 王洪武 等."肿瘤微创治疗技术".《肿瘤微创治疗技术》.北京科学技术出版社,2007,(第1版),第666-669，672-679，686，689，692页. |
| 王洪武 等."肿瘤微创治疗技术".《肿瘤微创治疗技术》.北京科学技术出版社,2007,(第1版),第666-669,672-679,686,689,692页. * |
| 顾瑛 等."新型光敏剂——血卟啉单甲醚临床应用研究的初步报道".《中国激光医学杂志》.1993,第2卷(第4期),第235-236页. |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101467996A (en) | 2009-07-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Hall et al. | Effects of hyperthermia on bladder cancer | |
| Roussakow | The history of hyperthermia rise and decline | |
| Cai et al. | Photodynamic therapy for intractable bronchial lung cancer | |
| CN103191427A (en) | Application of fullerene and derivant thereof to preparation of drug for treating skin disease or tumor under radio frequency or micro-wave irradiation | |
| Marcus | Photodynamic therapy of human cancer: clinical status, potential, and needs | |
| CN107638568B (en) | Biodegradable black phosphorus-based radiotherapy sensitizer and preparation method and application thereof | |
| CN101467996B (en) | Use of deuteroporphyrin derivates | |
| EP0533585A1 (en) | Method and apparatus for regulating and improving the status of development and survival of living organisms | |
| CN104971365B (en) | The new application of nano carbon mixed suspension injection | |
| Xue et al. | Optimal light dose and drug dosage in the photodynamic treatment using PHOTOCYANINE | |
| CN103040864B (en) | Medical application of selenium phosphate compound | |
| CN103143013B (en) | Photosensitive medicinal preparation containing amino poly-carboxylic acid modification tetraphenylporphyrin compound and purpose thereof | |
| CN106265722A (en) | The application in prevention and control of cancer of the ozone carburetion | |
| CN107715110B (en) | Biodegradable black phosphorus-based X-ray photodynamic therapy photosensitizer and preparation method and application thereof | |
| CN106362147B (en) | The preparation and application of the pharmaceutical composition of NO donator type titanium dioxide derivative | |
| Li et al. | ALA-or Ce6-PDT induced phenotypic change and suppressed migration in surviving cancer cells | |
| Jin et al. | Analysis of haematoporphyrin derivative and laser photodynamic therapy of upper gastrointestinal tumours in 52 cases | |
| Zhang et al. | Photodynamic therapy combined with local chemotherapy for the treatment of advanced esophagocardiac carcinoma | |
| CN101485660B (en) | Anti-tumor use of alpha-(8-quinolinoxy) monosubstituted phthalocyanine zinc | |
| JP6321298B2 (en) | Use of α- (8-quinolinyloxy) monosubstituted phthalocyanine zinc for treating psoriasis | |
| CN101190329B (en) | Medicinal composition for regrouping human P43 protein and its application in medication | |
| CN1111422C (en) | Injection for treating piles and its preparing process | |
| Cai et al. | A Case of Photodynamic Therapy for Advanced Adenocarcinoma of Esophagogastric Junction | |
| CN101485654B (en) | Application of T-2 toxin in preparing medicament for treating solid tumor | |
| CN101940565B (en) | Application of T-2 toxin in preparing drug for treating prostatic cancer |
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 |