CN110075298A - A kind of pharmaceutical composition for photodynamic therapy breast cancer - Google Patents
A kind of pharmaceutical composition for photodynamic therapy breast cancer Download PDFInfo
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- CN110075298A CN110075298A CN201910294305.0A CN201910294305A CN110075298A CN 110075298 A CN110075298 A CN 110075298A CN 201910294305 A CN201910294305 A CN 201910294305A CN 110075298 A CN110075298 A CN 110075298A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
- A61K41/0071—PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
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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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Abstract
The present invention relates to pharmaceutical technology fields, and in particular to a kind of pharmaceutical composition for photodynamic therapy breast cancer, it includes the purpurines 18 and pharmaceutically acceptable carrier of unit dose.The invention further relates to the methods for using the pharmaceutical composition and being treated by illumination to patient with breast cancer.Pharmaceutical composition of the invention is using this low toxicity of purpurine 18, efficient photosensitizer as pharmaceutically active agents, and treatment method of the invention uses the light of 630-700nm wavelength, has preferable skin-penetrating.After patient with breast cancer takes pharmaceutical composition of the invention, purpurine 18 reaches tumor of breast lesion, and under the irradiation of light source, purpurine 18 is generated reactive oxygen species by excitation, destroys mitochondria and endoplasmic reticulum in breast cancer cell, makes Apoptosis of Breast Cancer.Therefore, the present invention provides a kind of minimally invasive, less toxic, efficient photodynamic therapy new tool for breast cancer treatment.
Description
Technical field
The present invention relates to pharmaceutical technology fields, and in particular to a kind of pharmaceutical composition for photodynamic therapy breast cancer
Object.
Background technique
Breast cancer is one of women major cancers, and the body and mental health to women all cause to seriously affect.Traditional
Breast cancer treatment method mainly has operation, radiation and chemotherapy etc., but traditional treatment method respectively has advantage and disadvantage.Operation is answered at first
It uses in breast cancer treatment, but it is traumatic larger, and influence appearance.Radiotherapy is a kind of method of local treatment, is easy to draw
Play the side effects such as fatigue, skin injury, nausea and bone marrow suppression.Chemotherapy is the method for systematic treating, and the side effect of chemotherapy is main
Including alopecia, nausea, fatigue and immunity degradation etc..The method that these problems force people to find novel therapeutic breast cancer.
Photodynamic therapy (photodynamic therapy, PDT) is that a kind of clinical treatment malignant tumour has efficacious prescriptions
Method.In photodynamic therapy, the photoactivation photosensitive drug of certain wavelength can produce the reactive oxygen species with strong oxidizing property
(reactive oxygen species, ROS) mainly includes singlet oxygen, oxygen radical or peroxide.These active oxygens
The accumulation of substance can destroy the organelles such as mitochondria, lysosome, endoplasmic reticulum and nuclear membrane in tumour cell, so as to cause
The irreversible damage of tumour cell.Relative to traditional treatment means, photodynamic therapy is a kind of relatively minimally invasive, less toxic great
The anti-cancer methods of prospect.
Summary of the invention
The object of the present invention is to provide a kind of new tools for passing through photodynamic therapy breast cancer using purpurine 18, to keep away
Exempt from the apparent side effect of existing breast cancer treatment method.The present invention is a kind of for photodynamic therapy breast cancer by providing
Pharmaceutical composition realizes above-mentioned purpose.
Therefore, the present invention provides a kind of pharmaceutical composition for photodynamic therapy breast cancer, the pharmaceutical composition packet
Purpurine 18 and pharmaceutically acceptable carrier containing unit dose.
The molecular formula of purpurine 18 is C33H32N4O5, molecular weight 564.64, structural formula is as shown in following formula I:
Purpurine 18 is a kind of a kind of less toxic, efficient photosensitizer of photosensitive drug that photosensitive activity is strong, in visible light region
Maximum light absorption wavelength is located at 670nm, can produce the active oxygen of singlet oxygen, oxygen radical or peroxide etc under light illumination
Substance, can destroy the mitochondria in breast cancer cell structure and function, especially breast cancer cell and endoplasmic reticulum structure and
Function, to kill breast cancer cell.Therefore, purpurine 18 is the pharmaceutically active agents in pharmaceutical composition of the present invention.
The term as used herein " unit dose " refers to the non-toxic of the pharmaceutical composition single administration.Unit dose is logical
It is often 0-1 μM, it is therefore preferable to 0.25-0.75 μM, more preferable 0.5 μM.
Pharmaceutically acceptable carrier is used to be configured to pharmaceutical composition of the invention to be suitable for the dosage form of application.The present invention
The dosage form of pharmaceutical composition generally use oral preparation or ejection preparation.
For oral preparation, pharmaceutically acceptable carrier is pharmaceutically acceptable excipient, such as binder, filler, is collapsed
Agent, lubricant are solved, this is well known to technical field of medicine.Oral preparation is usually the form of tablet or capsule, one
It include the pharmaceutical composition of unit dose in tablet or a capsule.
For ejection preparation, pharmaceutically acceptable carrier is pharmaceutically acceptable injection liquid, and usual water for injection, this is
Well known to technical field of medicine.Include the pharmaceutical composition of unit dose in one ejection preparation.
The present invention also provides a kind of method for treating breast cancer, this method includes that medicine of the invention is applied to patient with breast cancer
Compositions, and lighting process is carried out to mammary gland.
Applying pharmaceutical composition of the invention to patient with breast cancer includes allowing patient with breast cancer's pharmaceutical composition of the present invention
Oral tablet or capsule, or the ejection preparation of pharmaceutical composition of the present invention is injected to patient with breast cancer.
After applying pharmaceutical composition of the invention to patient with breast cancer 2-3 hours, the mammary gland of patient with breast cancer is carried out
Light irradiation.In general, using the LED light source for the light that can issue 630-700nm wavelength, with 100-120J/cm2Optical power density
Mammary gland is irradiated 10 minutes to 30 minutes.According to patient to the tolerance degree of photo-thermal, appropriate adjustment dosage and irradiation time.
It can be using the intermittent lighting process method for stopping a period of time after irradiation a period of time.
In general, patient with breast cancer's daily administration pharmaceutical composition of the invention and to carry out lighting process primary.Treatment course
It is different according to the difference of patient with breast cancer, the reduction of breast cancer cell can be inspected periodically, determines the length and treatment of the course for the treatment of
Terminate.
Pharmaceutical composition of the invention using this low toxicity of purpurine 18, efficient photosensitizer as pharmaceutically active agents, and
Treatment method of the invention uses the light of 630-700nm wavelength, has preferable skin-penetrating.Patient with breast cancer takes this hair
After bright pharmaceutical composition, purpurine 18 reaches tumor of breast lesion, and under the irradiation of light source, purpurine 18 is generated by excitation
Reactive oxygen species destroy mitochondria and endoplasmic reticulum in breast cancer cell, make Apoptosis of Breast Cancer.Therefore, the present invention is cream
Gland cancer treatment provides a kind of minimally invasive, less toxic, efficient photodynamic therapy new tool.
Detailed description of the invention
Fig. 1 is that the smooth power of purpurine 18 kills the breast cancer cell containing hormone receptor in the display embodiment of the present invention 1
The photo of effect, wherein a is blank control group, the breast cancer cell in this group both without being handled with purpurine 18, also not into
Row lighting process；B is simple 18 processing group of purpurine, this group of breast cancer cell only uses purpurine 18 to handle, but without carrying out light
According to processing；C is simple lighting process group, this group of breast cancer cell only carries out lighting process, but without being handled with purpurine 18；d
For light power processing group, this group of breast cancer cell was not only handled with purpurine 18, but also carried out lighting process；Length of the scale is
100μm；
Fig. 2 is the photograph for showing the effect of the smooth power of purpurine 18 kill triple negative breast cancer cell in the embodiment of the present invention 2
Piece, wherein a is blank control group, and the breast cancer cell in this group with purpurine 18 both without being handled, also without carrying out at illumination
Reason；B is simple 18 processing group of purpurine, this group of breast cancer cell only uses purpurine 18 to handle, but without carrying out lighting process；c
For simple lighting process group, this group of breast cancer cell only carries out lighting process, but without being handled with purpurine 18；D is light power
Processing group, this group of breast cancer cell were not only handled with purpurine 18, but also carried out lighting process；Length of the scale is 100 μm.
Specific embodiment
Below by way of specific specific example and the embodiment of this patent is described with reference to the drawings.Those skilled in the art can
Understand other advantages and effect of this patent easily by content disclosed by this specification.This patent can also be by addition not
Same specific embodiment is embodied or practiced, and the various details in this specification can also be based on different viewpoints and application,
Various modifications or alterations are carried out under the spirit without departing from this patent.
Embodiment 1
This example demonstrates that the smooth power of purpurine 18 kills the breast cancer cell containing hormone receptor.
Used purpurine 18 is obtained from Shanghai Xian Hui Pharmaceutical Technology Co., Ltd, the used cream containing hormone receptor
Adenocarcinoma cell is MCF-7 Breast Cancer Cell, is obtained from American type culture collection.
Firstly, culture breast cancer cell.MCF-7 Breast Cancer Cell containing hormone receptor is used and contains 10% fetal calf serum
(FBS) RPMI-1640 culture solution routine culture is in containing 5%CO237 DEG C of incubators in cultivate 48 hours.
Then, breast cancer cell is handled with purpurine 18.By 5 × 103A breast cancer MCF-7 in fast growing period is thin
Born of the same parents plant into 24 holes in 96 orifice plates.After overnight, it is divided into blank control group, 18 processing group of simple purpurine, simple light and shines
Processing group and light power processing group are handled, and wherein blank control group and simple lighting process group are added without serum
RPMI-1640 basic culture solution, simple 18 processing group of purpurine and light power processing group be added containing 0.5 μM of purpurine 18 and
RPMI-1640 basic culture solution without serum.Each group breast cancer cell is incubated for 16 hours in 37 DEG C of incubators, this process
It needs to be protected from light.
Then, lighting process is carried out to MCF-7 Breast Cancer Cell.It is cultivated completely with the fresh RPMI-1640 containing FBS
Liquid replaces the culture solution in 96 orifice plates.Then, in addition to blank control group, with the 630nm radiation of visible light of LED light source remaining
Three groups, power density 105mW/cm2, action time 35s.Purpurine 18, which is excited, during this generates reactive oxygen species.
After acting on 35s, the basic apoptosis of MCF-7 Breast Cancer Cell in light power processing group, as shown in Figure 1 d, and the mammary gland of its excess-three group
The variation of cancer MCF-7 cellular morphology is little, as illustrated by figures 1 a-1 c.The experiment proves that purpurine 18 generates reactive oxygen species through illumination,
The structure and function that the MCF-7 Breast Cancer Cell containing hormone receptor can be destroyed, leads to the cancer cell death.
Embodiment 2
This example demonstrates that the smooth power of purpurine 18 kills triple negative breast cancer cell.Triple negative breast cancer refers to cancerous tissue
Immunohistochemical detection result is estrogen receptor (ER), progesterone receptor (PR) and proto-oncogene Her-2 are negative
Breast cancer.
Used purpurine 18 is obtained from Shanghai Xian Hui Pharmaceutical Technology Co., Ltd, used triple negative breast cancer cell
For triple negative breast cancer 4T1 cell, it is obtained from American type culture collection.
Firstly, purpurine 18 and breast cancer 4T1 cell are incubated for jointly.By breast cancer 4T1 cell seeding into 96 orifice plates
24 holes in, be divided into blank control group, 18 processing group of simple purpurine, simple lighting process group and light power processing group carry out
Processing, wherein the DMEM basic culture solution for being free of serum, simple purpurine 18 is added in blank control group and simple lighting process group
Processing group and light power processing group are added containing 0.5 μM of purpurine 18 and are free of the DMEM basic culture solution of serum.By each group
Breast cancer cell is incubated for 16 hours in 37 DEG C of incubators, this process needs are protected from light.
Then, lighting process is carried out to breast cancer 4T1 cell.With the fresh DMEM complete culture solution replacement containing FBS
Fall the culture solution in 96 orifice plates.Then, in addition to blank control group, with its excess-three group of the 630nm radiation of visible light of LED light source,
Power density is 105mW/cm2, action time 35s.Purpurine 18, which is excited, during this generates reactive oxygen species.Effect
After 35s, the basic apoptosis of breast cancer 4T1 cell in light power processing group, as shown in Figure 2 d, and the breast cancer 4T1 of its excess-three group
Cellular morphology variation is little, as shown in figs. 2 a-2 c.The experiment proves that purpurine 18 generates reactive oxygen species through illumination, can destroy
The structure and function of breast cancer 4T1 cell containing hormone receptor, leads to the cancer cell death.
The principles and effects of this patent are only illustrated in above-described embodiment, not for limitation this patent.It is any ripe
The personage for knowing this technology can all carry out modifications and changes to above-described embodiment under the spirit and scope without prejudice to this patent.Cause
This, those of ordinary skill in the art is complete in spirit revealed without departing from this patent and institute under technical idea such as
At all equivalent modifications or change, should be covered by the claim of this patent.
Claims (9)
1. a kind of pharmaceutical composition for photodynamic therapy breast cancer, which is characterized in that described pharmaceutical composition includes single
The purpurine 18 and pharmaceutically acceptable carrier of position dosage.
2. pharmaceutical composition according to claim 1, which is characterized in that the unit dose is 0-1 μM.
3. pharmaceutical composition according to claim 2, which is characterized in that the unit dose is 0.25-0.75 μM.
4. pharmaceutical composition according to claim 2, which is characterized in that the unit dose is 0.5 μM.
5. pharmaceutical composition described in any one of -4 according to claim 1, which is characterized in that described pharmaceutical composition is oral
The form of preparation.
6. pharmaceutical composition according to claim 5, which is characterized in that the oral preparation is tablet.
7. pharmaceutical composition according to claim 5, which is characterized in that the oral preparation is capsule.
8. pharmaceutical composition described in any one of -4 according to claim 1, which is characterized in that described pharmaceutical composition is injection
The form of preparation.
9. pharmaceutical composition according to claim 8, which is characterized in that the ejection preparation is with water for injection for the medicine
Acceptable carrier on.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910294305.0A CN110075298A (en) | 2019-04-12 | 2019-04-12 | A kind of pharmaceutical composition for photodynamic therapy breast cancer |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201910294305.0A CN110075298A (en) | 2019-04-12 | 2019-04-12 | A kind of pharmaceutical composition for photodynamic therapy breast cancer |
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| CN201910294305.0A Pending CN110075298A (en) | 2019-04-12 | 2019-04-12 | A kind of pharmaceutical composition for photodynamic therapy breast cancer |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1256126A (en) * | 1999-10-28 | 2000-06-14 | 许德余 | Composite medicine for optical dynamic treatment of tumor |
| CN108324958A (en) * | 2018-05-17 | 2018-07-27 | 陕西师范大学 | A kind of preparation method of purpurine 18- liposome nano vesicles and the application in preparing for tumor |
-
2019
- 2019-04-12 CN CN201910294305.0A patent/CN110075298A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1256126A (en) * | 1999-10-28 | 2000-06-14 | 许德余 | Composite medicine for optical dynamic treatment of tumor |
| CN108324958A (en) * | 2018-05-17 | 2018-07-27 | 陕西师范大学 | A kind of preparation method of purpurine 18- liposome nano vesicles and the application in preparing for tumor |
Non-Patent Citations (3)
| Title |
|---|
| ANNA DI STEFANO ET AL: "Purpurin-18 in Combination with Light Leads to Apoptosis or Necrosis in HL60 Leukemia Cells", 《PHOTOCHEMISTRY AND PHOTOBIOLOGY》 * |
| 张奇 编: "《军用药物制剂工程学》", 30 April 2012, 北京理工大学出版社 * |
| 沈卫镝 等: "叶绿素a降解产物紫红素-18的光动力效应", 《中国医药工业杂志》 * |
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Application publication date: 20190802 |
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