WO2015154547A1 - 纳米炭混悬注射剂的新用途 - Google Patents

纳米炭混悬注射剂的新用途 Download PDF

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WO2015154547A1
WO2015154547A1 PCT/CN2015/000250 CN2015000250W WO2015154547A1 WO 2015154547 A1 WO2015154547 A1 WO 2015154547A1 CN 2015000250 W CN2015000250 W CN 2015000250W WO 2015154547 A1 WO2015154547 A1 WO 2015154547A1
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module
nano
carbon
infrared
anticancer drug
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PCT/CN2015/000250
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French (fr)
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唐小海
邱宇
冉茂盛
黄源芳
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重庆莱美药业股份有限公司
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Priority claimed from CN201420175452.9U external-priority patent/CN203987988U/zh
Priority claimed from CN201420175822.9U external-priority patent/CN203987989U/zh
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/44—Elemental carbon, e.g. charcoal, carbon black
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/243—Platinum; Compounds thereof
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • 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
    • A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Definitions

  • the invention relates to the field of medicine and medical equipment thereof, and relates to a novel use of a nano carbon suspension injection, in particular to a medicament for preparing a cancer diagnostic reagent and a hyperthermia reagent for use with Near Infrared (NIR).
  • NIR Near Infrared
  • Application and a nano-carbon lymphography imager and a cancer thermochemotherapy device that can be used in combination with a nano-carbon suspension injection.
  • Chinese patent application CN 1458185A, patent number: ZL02113731.5, invention name: a preparation method of nano carbon suspension composition discloses preparation of nano carbon suspension for regional drainage lymph node for tracking malignant tumor method.
  • the nano-carbon suspension injection is a lymphatic tracer which is widely used to trace the distribution and distribution of lymph nodes in malignant tumors, and is clinically applied to the diagnosis process by using the targeting characteristics, that is, the stained cancer tissue is observed during surgery and It is impregnated with lymphoid tissue to determine the degree of metastasis of cancer cells, which helps to completely remove the invasive tissue of cancer cells during surgery.
  • this treatment also has some defects, such as producing surgical wounds, healing time is longer, giving patients physical and mental health. It brings great pain, and the cost of surgery is high, which will also bring a heavy financial burden to the patients. Therefore, it is urgent to develop some tumor treatment methods with less trauma, low cost, short cycle, better effect and lower toxic side effects.
  • Photothermal therapy is a new type of tumor treatment method developed recently. It has great application prospects due to its small trauma, obvious therapeutic effect and lower toxic side effects.
  • thermotherapy reagents carbon nanotubes, graphene, carbon quantum dots and fullerenes are the hotspots in current research.
  • the carbon atoms in these materials are hybridized with SP 2 to form a covalent bond and extend to the periphery to form a honeycomb six-membered ring structure.
  • the ⁇ electrons on the ring are enriched to form a large delocalized ⁇ bond, so SP 2 hybridization imparts these carbons.
  • the material has many special properties, including the ability to absorb NIR light.
  • thermotherapy reagents can quickly convert light energy into heat after absorbing NIR, killing tumor cells, and thus are ideal candidates for thermal therapy.
  • thermotherapy reagents After a long period of scientific research data accumulation, the development of thermotherapy reagents has made great progress. Among them, effective improvement of thermal conversion efficiency, surface modification to improve targeting and toxicity research have made some progress, but there are also many problems in the research process. , limited clinical application, mainly has the following defects:
  • the preparation process is difficult to control.
  • Carbon nanotubes, graphene, and fullerenes have many crude impurities, which may cause toxic side reactions in the body, poor hydrophilicity, and are not conducive to dispersion in water, so refining and surface modification are required.
  • the refining process mainly removes impurities, improves the purity, and reduces the risk of toxic side effects of impurities.
  • the surface modification is mainly to modify the surface group of carbon, which is beneficial to disperse in water and improve the conversion efficiency of NIR in the hyperthermia process.
  • the carbon nanotubes have a tubular structure, and the two ends of the preparation process need to be passivated, but usually the treatment may be incomplete, and there are some tips like needle tips. After the application, these sharp ends It is easy for the head to puncture the vessel wall and then enter the nucleus with potential genotoxicity.
  • the first technical problem to be solved by the present invention is to provide a new use of a nano-carbon suspension injection, in particular to a medicament for preparing a cancer diagnostic reagent and a hyperthermia reagent for use with Near Infrared (NIR). application.
  • NIR Near Infrared
  • the inventors first proposed the use of nano-carbon suspension injection to trace the characteristics of lymph node drainage and distribution (lymphatic tropism) of malignant tumors, using near-infrared light heating to diagnose tissue, due to nanometer
  • the carbon suspension injection can effectively absorb infrared rays and convert it into heat, thereby causing a large temperature difference between the cancer cells and the normal cells, and the normal cell temperature does not change at about 37 ° C; while the cancer tissue with nano carbon absorbs heat.
  • the temperature reached 53-55 ° C, the cancer cells and normal cells were distinguished by thermal imager, and the distribution and metastasis of cancer cells were judged.
  • the public was provided with a non-invasive diagnosis of cancer cells and malignant tumors by using nano-carbon suspension injection. And new methods of distribution.
  • the inventors have also provided the targeting of lymphatic tracers using nano-carbon suspension injections, and the nano-carbon suspension injections can effectively absorb the characteristics of infrared rays converted into heat, and are diagnosed as cancerous cells by near-infrared heating.
  • the tissue and parts make the temperature of cancer cells rise rapidly, and are killed by high temperature at 50-56 °C, while normal cells are at a level acceptable to human body in a short time, achieving the primary site of malignant tumor and its lymphatic metastasis the goal of.
  • the near-infrared light used has a wavelength of 780-2600 nm, preferably a wavelength of 785-1400 nm; an energy of 0.5-7680 J/cm 2 , preferably an energy of 60-4590 J/cm 2 .
  • the nano-carbon suspension injection according to the present invention is prepared according to the method described in the invention patent of the invention of the Chinese patent application CN 1458185A (Patent No.: ZL02113731.5), which is a preparation method of a nano-carbon suspension composition.
  • the nano carbon suspension injection is composed of nano carbon, PVP, physiological saline and a pH adjuster, wherein the nano carbon has a particle diameter of 50-250 nm.
  • the particle size ranges from 100 to 150 nm.
  • Each 1000ml of nano-carbon suspension injection contains 2.5-200g of nano-carbon, 2-200g of polyvinylpyrrolidone (PVP), pH adjuster to adjust the pH to 6.5-8.0, and the balance is physiological saline.
  • PVP polyvinylpyrrolidone
  • each 1000 ml of the nano-carbon suspension injection contains 50 g of nano-carbon, 20 g of polyvinylpyrrolidone (PVP), and a pH adjuster to adjust the pH to 7.0, and the balance is physiological saline.
  • the nano carbon is obtained by removing carbon-soluble impurities from the carbon black through an organic solvent, drying and removing organic residues; pickling and alkali washing to remove inorganic impurities; and washing to remove acid, alkali and inorganic residues to obtain a dry residue.
  • the pH adjusting agent may be any chemical substance that can adjust pH, including sodium citrate, citric acid, sodium hydroxide, hydrochloric acid, acetic acid, tartaric acid, and lactic acid.
  • the most suitable pH adjusting agent is sodium citrate.
  • One of the preparation methods of the nano carbon suspension injection according to the present invention weigh 50 g of polyvinylpyrrolidone (preferably PVP K30), dissolve it in 300 ml of physiological saline; weigh 20 g of nano carbon, and add it to the solution of polyvinylpyrrolidone under stirring. Further, physiological saline was added to 1000 ml; it was added to a vibrating mill; the mixture was shaken at room temperature for 5 minutes; and the pH was adjusted to 6.5-8.0 with 1 mol/L sodium citrate.
  • polyvinylpyrrolidone preferably PVP K30
  • physiological saline was added to 1000 ml; it was added to a vibrating mill; the mixture was shaken at room temperature for 5 minutes; and the pH was adjusted to 6.5-8.0 with 1 mol/L sodium citrate.
  • One of the preparation methods of the nano carbon suspension injection of the invention weigh polyvinylpyrrolidone K30 50g, dissolved in 300ml of physiological saline; weigh 20g of nano-carbon, add to the solution of polyvinylpyrrolidone under stirring, continue to add physiological saline to 1000ml; add to the ball mill; ball mill dispersion for 96 hours at room temperature; adjust pH with 1mol / L sodium citrate To 6.5-8.0.
  • a nano-carbon suspension injection may be mixed with an anticancer drug.
  • the anticancer drugs that can be used together are doxorubicin, epirubicin, cisplatin, paclitaxel, and 5-fluorouracil (5-FU).
  • a novel anticancer pharmaceutical composition which comprises the following components by weight: 0.03125-32 parts of anticancer drug, 0.5-400 parts of nano carbon;
  • the preferred ratio range is: 0.125-8 parts of anticancer drug, 1-100 parts of nano carbon;
  • the optimal ratio 1 part of anticancer drug, 5 parts of nano carbon.
  • the anticancer drug is doxorubicin, epirubicin, cisplatin, paclitaxel, 5-fluorouracil (5-FU); preferably doxorubicin.
  • the cell test by hyperthermia showed that there was no effect on the cells after the cells were added with nano-carbon without near-infrared light irradiation and the cells were not irradiated with near-infrared light.
  • the temperature at 35 °C and 37 °C had no effect on the cells.
  • the inhibition rate on the cells gradually increases.
  • the temperature reaches 53 ° C the inhibition rate on the cells reaches 90% or more.
  • the temperature was 42 °C
  • the addition of five drugs doxorubicin, epirubicin, cisplatin, paclitaxel, 5-FU
  • the inhibition rate of 1 ⁇ g/ml doxorubicin was equivalent to the inhibition rate of 4 ⁇ g/ml doxorubicin.
  • the second technical problem solved by the present invention is to provide a nano-carbon lymphography imager, which can increase the corresponding software application when used, and can effectively, conveniently and accurately detect the information such as the number, distribution and orientation of lymph nodes.
  • the nano-carbon suspension injection used in combination with the present invention is used for the preparation of a medicament for use in a cancer diagnostic reagent for use with near-infrared light.
  • the nano carbon lymphography imager comprises a detection module, and further comprises an infrared emission module, a time control module, a data acquisition module, a processing module, a storage module, a comparison module and a display module, and the time control module, the data acquisition module and the storage module
  • the display module is respectively connected to the processing module
  • the detecting module is connected to the data collecting module
  • the infrared transmitting module is connected to the time control module
  • the comparing module is respectively connected with the storage module and the display module.
  • the infrared emitting module is an infrared light emitting diode array.
  • the nano-carbon lymphography imager further includes a prompting module, and the prompting module is connected to the comparing module.
  • the prompting module is an LED light.
  • the detecting module is an infrared receiver.
  • the display module is a three-dimensional image display device.
  • the beneficial effect of the nano-carbon lymphography imager of the invention is that when the nano-carbon suspension is injected around the cancer cell disease, the nano-carbon is emitted by adding corresponding software application and using the infrared emission module in the nano-carbon lymphography imager to emit infrared rays.
  • Absorbing infrared temperature rises when it forms a temperature difference with the surrounding human tissue, and detects infrared radiation through the detection module, and converts it into an electrical signal for transmission to the data acquisition module, and the data acquisition module transmits the collected data to the data acquisition module, and the data acquisition module pairs
  • the data is processed correspondingly to obtain a corresponding display image, and the storage module performs corresponding time on the displayed image. Store and compare through the comparison module.
  • the processing module is connected with the infrared transmitting module through the time control unit to realize automatic control of the infrared transmitting module, and the time control unit enables the infrared transmitting module to accurately control the infrared emitting time and avoid the error of human operation.
  • the third technical problem solved by the present invention is to provide a cancer thermochemotherapy apparatus, which can increase the corresponding software application when used, and can effectively, conveniently and accurately detect the number, distribution and orientation of lymph nodes, and obtain the above information. It can effectively achieve the effect of precise cancer thermochemotherapy on lymph nodes.
  • the invention relates to the application of the nano carbon suspension injection used in the invention to prepare a medicament for the cancer hyperthermia reagent used in combination with near-infrared light.
  • the cancer thermal chemotherapy device of the invention comprises a detection module, an infrared emission module, a high-power infrared emission module, a temperature detection module, a time control module, a data acquisition module, a processing module, a storage module, a comparison module and a display module, and the temperature detection module
  • the time control module, the data acquisition module, the storage module and the display module are respectively connected to the processing module
  • the detection module is connected with the data acquisition module
  • the infrared emission module and the high-power infrared emission module are respectively connected with the time control module
  • the comparison module respectively
  • the storage module and the display module are connected.
  • the infrared emitting module is an infrared light emitting diode array.
  • the cancer thermochemotherapy apparatus further includes a prompting module, and the prompting module is connected to the comparing module.
  • the prompting module is an LED light.
  • the detecting module is an infrared receiver.
  • the display module is a three-dimensional image display device.
  • the beneficial effect of the cancer thermochemotherapy apparatus of the present invention is that when the nano carbon suspension is injected around the cancer cell disease, the nano carbon absorbs the infrared rays by increasing the corresponding software application and using the infrared emission module in the cancer thermochemometer to emit infrared rays.
  • the infrared radiation detection is performed through the detection module, and is converted into an electrical signal and transmitted to the data acquisition module, and the data acquisition module transmits the collected data to the data acquisition module, and the data acquisition module performs the data on the data acquisition module.
  • the corresponding display image is obtained.
  • the high-power infrared emission module is used to warm the surrounding area of the lesion.
  • the nano-carbon is more capable of converting infrared rays into heat than other normal tissues of the human body, that is, after heating, after entering the draining lymph node.
  • the temperature of the nano-carbon can be warmed up faster than other normal tissues of the body.
  • the lymph nodes of the lesion can be subjected to thermochemotherapy.
  • the temperature detection model can be used to detect the lymph nodes of the lesion and other normal tissues of the human body to ensure the killing. Cancer cells do not destroy other normal tissues of the human body.
  • the infrared transmitting module and the high-power infrared transmitting module are respectively connected with the time control module to realize automatic control of the infrared transmitting module and the high-power infrared transmitting module, and the time control unit enables the infrared transmitting module and the high-power infrared transmitting module to be accurately controlled.
  • Launch time to avoid errors in human operation.
  • the storage module stores the corresponding images at different times and before and after the chemotherapy, and compares them through the comparison module. When comparing the images at different times or before and after the chemotherapy, the chemotherapy is effective or the lesions are transferred. At this time, different images are displayed in time and the user is prompted by the prompting module, so as to timely notify the user that the chemotherapy is effective or the lesion has a metastasis effect, and avoiding the human neglect and causing serious consequences.
  • Figure 1 shows tumor volume growth curves for different treatment groups.
  • Figure 2 shows the survival rate of nude mice in different treatment groups.
  • Figure 3 shows the growth inhibitory effects of different treatment groups on metastatic lymph nodes.
  • Embodiment 4 is a structural view of Embodiment 1 of a nano-carbon lymphography imager.
  • Figure 5 is a structural view of Embodiment 2 of a nano-carbon lymphography imager.
  • Figure 6 is a structural view of Embodiment 3 of a cancer thermochemotherapy apparatus.
  • Figure 7 is a structural view of Example 4 of a cancer thermochemotherapy apparatus.
  • Nano carbon can effectively convert NIR into heat.
  • the attenuation of NIR through biological tissue is small compared to light of other wavelengths.
  • the ability to pass tissue is a condition for treating non-superficial tumors.
  • Nano-carbon enters the excited state in NIR, releasing vibration energy and converting it into heat can cause cell death.
  • Nano-carbon has a wide range of electromagnetic absorption, covering the entire wavelength of NIR I and II windows, and this wavelength is light for biological tissue. Through the window. It is also the wavelength of the radar and the wavelength of the microwave.
  • the nano carbon suspension injection combined with Near Infrared (NIR) as a cancer diagnostic reagent is an embodiment in which a nano carbon suspension is injected around a cancer lesion and enters the draining lymph node quickly (about less than 10 minutes).
  • the nano-carbon absorbs infrared light and heats up, and forms a detectable temperature difference with the surrounding normal tissue cells.
  • the thermal imager can visually reflect the important clinical information such as the number, distribution and orientation of the lymph nodes traced by the nano-carbon.
  • the embodiment of the nano carbon suspension injection combined with Near Infrared (NIR) as a hyperthermia reagent is to inject a nano carbon suspension into the periphery of the cancer lesion, and enter the draining lymph node quickly (about less than 10 minutes).
  • Cancer cells, nano-carbons absorb infrared rays and heat up, so that the temperature of cancer cells rises rapidly, and is killed by high temperature at 50-56 °C, while normal cells are at a level acceptable to human body in a short time, achieving the primary site of malignant tumors and The purpose of drainage lymphatic hyperthermia.
  • cancers such as breast cancer, brain cancer, cervical cancer, kidney cancer, liver cancer, prostate cancer, oral cancer, lymphoma, neuroendocrine cancer, and skin cancer.
  • the cells were mixed with DMEM medium, fetal bovine serum (FCS), cell digestive trypsin, penicillin streptomycin, phosphate buffer (PBS, pH 7.4).
  • FCS fetal bovine serum
  • PBS phosphate buffer
  • Nano-carbon suspension injection doxorubicin hydrochloride for injection (ie, doxorubicin, doxorubicin), epirubicin hydrochloride for injection (ie, epirubicin), cisplatin injection, paclitaxel injection, injection 5-fluorouracil (5-FU) was used.
  • Hyperthermia The cells in the 96-well plate were added with nano-carbon suspension injection to make the final concentration of nano-carbon 25 ⁇ g/ml. The cells were irradiated with near-infrared light for a period of time (1 ⁇ 10min), and the temperature was measured to make the temperature. After incubation for 35 hours at 35 °C, 37 °C, 42 °C, 45 °C, 50 °C, and 53 °C, the OD value was determined by adding CCK8 reagent for a certain period of time, and the inhibition rate of cells at different temperatures was calculated. After the cells were added with nano-carbon, there was no near-infrared light irradiation, and the cells were irradiated with near-infrared light without adding nano-carbon.
  • Doxorubicin hydrochloride for injection ie doxorubicin, doxorubicin: 1 ⁇ g/ml
  • Epirubicin hydrochloride for injection ie, epirubicin: 1 ⁇ g/ml
  • the inhibition rate also gradually increased, and when the temperature reached 53 ° C, the inhibition rate to cells reached 90% or more.
  • the temperature is 42 °C, the inhibition rate of the five drugs added to the nano-carbon after irradiation with near-infrared light is greatly improved.
  • the inhibition rate of 1 ⁇ g/ml doxorubicin was equivalent to the inhibition rate of 4 ⁇ g/ml doxorubicin.
  • the cells were mixed with DMEM medium, fetal bovine serum (FCS), cell digestive trypsin, penicillin streptomycin, phosphate buffer (PBS, pH 7.4).
  • FCS fetal bovine serum
  • PBS phosphate buffer
  • BaIB/c-nu mice female, 4 to 6 weeks old, weighing 20 ⁇ 2 g. Free drinking water and eating during the experiment. The daily light was 12h, and 5 mice/cage were kept in separate air supply cages.
  • mice Clean-grade inbred Kunming mice, female, 6-7 weeks old, weighing 20 ⁇ 2g. Free drinking water and eating during the experiment.
  • the mice (5/cage) cages were ventilated with a central ventilation system for 12 hours of daily light.
  • volume (length ⁇ width 2 )/2.
  • mice Extract the milky white ascites from H22 tumor-bearing mice, adjust the number of cells to 2 ⁇ 10 7 cells/mL, and inoculate 0.05 mL cell suspension under the skin of left hind foot of Kunming mice to obtain a mouse model of lymph node metastasis.
  • Mice were treated when the tumor diameter was 6-8 mm with neither ulceration nor necrosis.
  • the mice were randomly divided into 4 groups, 10 in each group, which were respectively nano-carbon laser irradiation group, nano-carbon group, laser irradiation group and negative control group (no nano-carbon, no laser).
  • mice After the mouse left hind limb footpad was injected subcutaneously with 0.05 ml nanocarbon solution for 10 min, the depilated skin at the axillary lymph node of the left hind limb of the mouse was irradiated with a 1064 nm laser for 5 min, and the laser power was 3 W/cm 2 .
  • the temperature of the tumor surface is detected after laser irradiation.
  • the average temperature rise of the laser irradiation group was 7.2 ⁇ 0.8°C, and the temperature increase of the nano-carbon laser irradiation group was 19.1 ⁇ 1.5°C.
  • the nano-carbon laser irradiation group has significant significance. Due to the death of nude mice, only 10 days of tumor volume was observed. The tumors in the nano-carbon group and the laser irradiation group continued to grow, and the tumor disappeared in the nano-carbon laser irradiation group (see Figure 1). By the 45th day, except for the nano-carbon laser irradiation group, all the other three groups of nude mice died (see Table 8, Figure 2).
  • nano-carbon can be used for lymphatic targeted hyperthermia.
  • the metastatic lymph node hyperthermia experiment established in the experiment also showed that the nano carbon enters the lymph node and is irradiated with laser, which can reduce the weight and volume of the metastatic lymph node and the coagulative necrosis of the tumor cell.
  • nano-carbon injection has no acute toxicity and ensured the safety of clinical medication.
  • nano-carbon suspension injection has been listed as a lymphatic tracer for nearly 10 years, and the number of patients in clinical use has reached more than 100,000. No adverse reactions have been reported so far, indicating that there is no local application of nano-carbon suspension injection. Toxicity further ensures the safety of clinical medication.
  • lymphatic metastasis of cancer cells means that the malignant tumor cells are detached from their original parts and spread to other parts of the body through direct spread, lymphatic, blood, and planting, and even proliferate and grow in multiple organs.
  • Lymphatic metastasis often occurs in patients with advanced cancer. Lymphatic metastasis is one of the important factors affecting the prognosis of malignant tumors. The fate of many cancer patients is often not determined by the primary tumor. Therefore, effective lymphadenectomy in the tumor drainage area is an important means to improve the quality of life of patients and prolong the life of patients.
  • the nano-carbon lymphography imager and the cancer thermochemotherapy apparatus provided by the invention can effectively cooperate with the nano-carbon suspension injection to realize the application of diagnosis and treatment.
  • the present invention provides a nano-carbon lymphography imager including detection
  • the module also includes an infrared transmitting module, a time control module, a data acquisition module, a processing module, a storage module, and a comparison module.
  • the block and display module, the time control module, the data acquisition module, the storage module and the display module are respectively connected with the processing module, the detection module is connected with the data acquisition module, the infrared emission module is connected with the time control module, and the comparison module is separately stored and stored.
  • the module and the display module are connected.
  • the nano-carbon When the nano-carbon suspension is injected around the cancer cell disease, the nano-carbon absorbs the infrared light by adding corresponding software application and using the infrared emission module in the nano-carbon lymphograph to emit infrared rays. When it forms a temperature difference with the surrounding human tissue The infrared radiation detection is detected by the detection module, and converted into an electrical signal and transmitted to the data acquisition module.
  • the data acquisition module transmits the collected data to the processing module, and the processing module processes the data accordingly to obtain a corresponding display image, and the storage module displays The image is stored for the corresponding time and compared by the comparison module. When comparing the images at different times, the lesions are shifted.
  • the processing module is connected with the infrared transmitting module through the time control unit to realize automatic control of the infrared transmitting module, and the time control unit enables the infrared transmitting module to accurately control the infrared emitting time and avoid the error of human operation.
  • the nano carbon lymphography imager of this example includes a detection module, and further includes an infrared emission module, a time control module, a data acquisition module, a processing module, a storage module, a comparison module, and a display module, and the time control module
  • the data acquisition module, the storage module and the display module are respectively connected to the processing module
  • the detection module is softly connected with the data acquisition module
  • the infrared transmission module is connected with the time control module
  • the comparison module is respectively connected with the storage module and the display module.
  • Carbon black (CB) has good biocompatibility, no toxic side effects, and has a large specific surface area, and can be targeted into the lymph node utilization.
  • a nano-carbon suspension is injected around the cancer cell disease, and after the nano-carbon suspension enters the draining lymph node, the infrared radiation module of the nano-carbon lymphography image detector is used to emit infrared rays to irradiate the human body.
  • the corresponding software application needs to be added, because the processing module in the nano-carbon lymphography imager of this example is connected to the infrared emission module through the time control module.
  • the automatic control of the infrared emission module can be realized, and the user can set the required irradiation time according to the need, thereby accurately controlling the infrared emission time of the infrared emission module to avoid the error of human operation.
  • the infrared emitting module is an infrared light emitting diode array. It can realize the launching requirements of different areas and different locations.
  • the nano carbon in the patient absorbs infrared rays and heats up to form a temperature difference with the surrounding human tissue.
  • the infrared radiation detection is performed by the detection module, and the detection information is converted into an electrical signal and transmitted to the data acquisition module, and the data acquisition module transmits the collected data to the processing module, and the processing module processes the data accordingly to obtain a corresponding display image.
  • the processing module transmits the display image to the display module for real-time display for the user to view.
  • the processing module transmits images of different time points to the storage module for storage.
  • the storage module transmits the stored image information to the comparison module for comparison, and the comparison module compares the images of different time electrics. When comparing the image differences at different time points, the image is transmitted to the display module, and the difference is displayed to the user for convenient viewing by the user. .
  • the display module can select a three-dimensional image display device, which is convenient and intuitive for the user to view.
  • the nano-carbon lymphography imager of this example adds a prompting module to the first embodiment.
  • the prompt module is connected to the comparison module. That is, the nano-carbon lymphography imager of this example, as shown in FIG. 5, includes a detection module, and further includes an infrared emission mode. a block, a time control module, a data acquisition module, a processing module, a storage module, a comparison module, a prompt module, and a display module, wherein the time control module, the data acquisition module, the storage module, and the display module are respectively connected to the processing module, and the detection module Connected to the data acquisition module, the infrared emission module is connected with the time control module, and the comparison module is respectively connected with the storage module, the prompt module and the display module.
  • the prompt module can display the prompt through the LED, or can prompt the user by sound or the like.
  • Carbon black (CB) has good biocompatibility, no toxic side effects, and has a large specific surface area, and can be targeted into the lymph node utilization.
  • a nano-carbon suspension is injected around the cancer cell disease, and after the nano-carbon suspension enters the draining lymph node, the infrared radiation module of the nano-carbon lymphography image detector is used to emit infrared rays to irradiate the human body.
  • the corresponding software application needs to be added, because the processing module in the nano-carbon lymphography imager of this example is connected to the infrared emission module through the time control module.
  • the automatic control of the infrared emission module can be realized, and the user can set the required irradiation time according to the need, thereby accurately controlling the infrared emission time of the infrared emission module to avoid the error of human operation.
  • the infrared emitting module is an infrared light emitting diode array. It can realize the launching requirements of different areas and different locations.
  • the nano carbon in the patient absorbs infrared rays and heats up to form a temperature difference with the surrounding human tissue.
  • the infrared radiation detection is performed by the detection module, and the detection information is converted into an electrical signal and transmitted to the data acquisition module, and the data acquisition module transmits the collected data to the processing module, and the processing module processes the data accordingly to obtain a corresponding display image.
  • the processing module transmits the display image to the display module for real-time display for the user to view.
  • the processing module transmits images of different time points to the storage module for storage.
  • the storage module transmits the stored image information to the comparison module for comparison, and the comparison module compares the images of different time electrics.
  • the comparison module compares the image differences at different time points, the image is transmitted to the display module, and the difference is displayed to the user for convenient viewing by the user. .
  • the comparison module compares the image differences at different time points, it indicates that the lesion has shifted, and the system prompts the user to view different points through the prompt module.
  • the display module can select a three-dimensional image display device, which is convenient and intuitive for the user to view.
  • the nano-carbon when the nano-carbon suspension is injected around the cancer cell disease, the nano-carbon absorbs the infrared light by adding corresponding software applications and using the infrared emission module in the nano-carbon lymphograph to emit infrared rays.
  • the human body tissue forms a temperature difference, it detects infrared radiation through the detection module, and converts it into an electrical signal and transmits it to the data acquisition module.
  • the data acquisition module transmits the collected data to the processing module, and the processing module processes the data accordingly to obtain a corresponding display image.
  • the storage module stores the corresponding time of the display image, and compares it through the comparison module. When comparing the images at different times, the lesions are shifted. At this time, different images are displayed in time and prompted by the prompting module.
  • the processing module is connected with the infrared transmitting module through the time control unit to realize automatic control of the infrared transmitting module, and the time control unit enables the infrared transmitting module to accurately control the infrared emitting time and avoid the error of human operation.
  • the invention provides a cancer thermochemotherapy apparatus, comprising a detection module, an infrared emission module, a high-power infrared emission module, a temperature detection module, a time control module, a data acquisition module, a processing module, a storage module,
  • the comparison module and the display module, the temperature detection module, the time control module, the data acquisition module, the storage module and the display module are respectively connected with the processing module, the detection module is connected with the data acquisition module, the infrared emission module and the high-power infrared emission module They are respectively connected to the time control module, and the comparison modules are respectively connected to the storage module and the display module.
  • the infrared light is absorbed by increasing the corresponding software application and using the infrared emission module in the cancer thermochemotherapy instrument, and the nano-carbon absorbs the infrared temperature when it forms a temperature difference with the surrounding human tissue.
  • the detection module performs infrared radiation detection and converts it into an electrical signal for transmission to the data acquisition module.
  • the data acquisition module transmits the collected data to the data acquisition module, and the data acquisition module processes the data accordingly to obtain a corresponding display image. After obtaining information such as the number, distribution and orientation of lymph nodes, the high-power infrared emission module is used to warm the surrounding area of the lesion.
  • the nano-carbon is more capable of converting infrared rays into heat than other normal tissues of the human body, that is, after heating, after entering the draining lymph node.
  • the temperature of the nano-carbon can be warmed up faster than other normal tissues of the body. With this property, the lymph nodes of the lesion can be subjected to thermochemotherapy.
  • the temperature detection model can be used to detect the lymph nodes of the lesion and other normal tissues of the human body to ensure the killing. Cancer cells do not destroy other normal tissues of the human body.
  • the infrared transmitting module and the high-power infrared transmitting module are respectively connected with the time control module to realize automatic control of the infrared transmitting module and the high-power infrared transmitting module, and the time control unit enables the infrared transmitting module and the high-power infrared transmitting module to be accurately controlled.
  • Launch time to avoid errors in human operation.
  • the storage module stores the corresponding images at different times and before and after the chemotherapy, and compares them through the comparison module. When comparing the images at different times or before and after the chemotherapy, the chemotherapy is effective or the lesions are transferred. At this time, different images are displayed in time and the user is prompted by the prompting module, so as to timely notify the user that the chemotherapy is effective or the lesion has a metastasis effect, and avoiding the human neglect and causing serious consequences.
  • the cancer thermochemotherapy instrument of this example includes a detection module, an infrared emission module, a high-power infrared emission module, a temperature detection module, a time control module, a data acquisition module, a processing module, a storage module, a comparison module, and a display.
  • the module, the temperature detecting module, the time control module, the data collecting module, the storage module and the display module are respectively connected with the processing module, the detecting module is connected with the data collecting module, the infrared transmitting module and the high-power infrared transmitting module are respectively controlled by time
  • the modules are connected, and the comparison modules are respectively connected to the storage module and the display module.
  • Carbon black (CB) has good biocompatibility, no toxic side effects, and has a large specific surface area, and can be targeted into the lymph node utilization.
  • a nano-carbon suspension is injected around the cancer cell disease, and after the nano-carbon suspension enters the draining lymph node, the infrared radiation module of the cancer thermochemotherapy device is used to emit infrared rays to irradiate the human body.
  • the processing module in the cancer thermochemotherapy instrument of this example is connected to the infrared transmitting module through the time control module.
  • the infrared emission module can be automatically controlled, and the user can set the required irradiation time according to the need, thereby accurately controlling the infrared emission time of the infrared emission module to avoid the error of human operation.
  • the infrared emitting module is an infrared light emitting diode array. It can realize the launching requirements of different areas and different locations.
  • the nano carbon in the patient absorbs infrared rays and heats up to form a temperature difference with the surrounding human tissue.
  • the infrared radiation detection is performed through the detection module, and the detection information is converted into an electrical signal and transmitted to the data acquisition module, and the data acquisition module transmits the collected data to the processing module, and the processing module pairs the data. Corresponding processing is performed to obtain a corresponding display image.
  • the high-power infrared emission module is used to warm the periphery of the lesion, and the nano-carbon is more capable of converting infrared rays into heat than other normal tissues of the human body, that is, After warming, the temperature of the nano-carbon after entering the draining lymph node can be warmed up faster than other normal tissues of the body.
  • the lymph node of the lesion can be subjected to thermochemotherapy, and the thermochemotherapy can simultaneously use the temperature detecting mold to the lymph nodes of the lesion and other normal tissues of the human body. Real-time temperature detection ensures that cancer cells are killed without destroying other normal tissues of the body.
  • the temperature detection module is an infrared receiving device that detects infrared radiation of the patient and can accurately know the temperature state of the lymph nodes and other normal human tissues. Once the normal tissue of the human body reaches 39 degrees, it is transmitted to the processing module, and the processing module commands high-power infrared emission. The module stops working and avoids errors in human operation.
  • the infrared transmitting module and the high-power infrared transmitting module are respectively connected with the time control module to realize automatic control of the infrared transmitting module and the high-power infrared transmitting module, and the time control unit enables the infrared transmitting module and the high-power infrared transmitting module to be accurately controlled.
  • the launch time also avoids the error of human operation.
  • the processing module transmits the display image to the display module for real-time display for the user to view.
  • the processing module transmits the images at different time points and images before and after the cancer thermochemotherapy to the storage module for storage.
  • the storage module transmits the stored image information to the comparison module for comparison, and the comparison module compares the images of different time electrics.
  • the module transmits the difference to the display module. For the user, it is convenient for the user to view.
  • the display module can select a three-dimensional image display device, which is convenient and intuitive for the user to view.
  • the cancer thermochemotherapy apparatus of this example adds a prompting module to the third embodiment.
  • the prompt module is connected to the comparison module. That is, the cancer thermochemotherapy instrument of this example, as shown in FIG. 7, includes a detection module, an infrared emission module, a high-power infrared emission module, a temperature detection module, a time control module, a data acquisition module, a processing module, a storage module, a comparison module, and a display module, the temperature detection module, the time control module, the data acquisition module, the storage module and the display module are respectively connected to the processing module, the detection module is connected with the data acquisition module, the infrared emission module and the high-power infrared emission module are respectively time and time The control module is connected, and the comparison module is respectively connected to the storage module, the prompt module and the display module.
  • the prompt module can display the prompt through the LED, or can prompt the user by sound or the like.
  • Carbon black (CB) has good biocompatibility, no toxic side effects, and has a large specific surface area, and can be targeted into the lymph node utilization.
  • a nano-carbon suspension is injected around the cancer cell disease, and after the nano-carbon suspension enters the draining lymph node, the infrared radiation module of the cancer thermochemotherapy device is used to emit infrared rays to irradiate the human body.
  • the processing module in the cancer thermochemotherapy instrument of this example is connected to the infrared transmitting module through the time control module.
  • the infrared emission module can be automatically controlled, and the user can set the required irradiation time according to the need, thereby accurately controlling the infrared emission time of the infrared emission module to avoid the error of human operation.
  • the infrared emitting module is an infrared light emitting diode array. It can realize the launching requirements of different areas and different locations.
  • the nano carbon in the patient absorbs infrared rays and heats up to form a temperature difference with the surrounding human tissue.
  • the infrared radiation detection is performed through the detection module, and the detection information is converted into an electrical signal and transmitted to the data acquisition module, and the data acquisition module transmits the collected data to the processing module, and the processing module pairs the data. Corresponding processing is performed to obtain a corresponding display image.
  • the high-power infrared emission module is used to warm the periphery of the lesion, and the nano-carbon is more capable of converting infrared rays into heat than other normal tissues of the human body, that is, After warming, the temperature of the nano-carbon after entering the draining lymph node can be warmed up faster than other normal tissues of the body.
  • the lymph node of the lesion can be subjected to thermochemotherapy, and the thermochemotherapy can simultaneously use the temperature detecting mold to the lymph nodes of the lesion and other normal tissues of the human body. Real-time temperature detection ensures that cancer cells are killed without destroying other normal tissues of the body.
  • the temperature detection module is an infrared receiving device that detects infrared radiation of the patient and can accurately know the temperature state of the lymph nodes and other normal human tissues. Once the normal tissue of the human body reaches 39 degrees, it is transmitted to the processing module, and the processing module commands high-power infrared emission. The module stops working and avoids errors in human operation.
  • the infrared transmitting module and the high-power infrared transmitting module are respectively connected with the time control module to realize automatic control of the infrared transmitting module and the high-power infrared transmitting module, and the time control unit enables the infrared transmitting module and the high-power infrared transmitting module to be accurately controlled.
  • the launch time also avoids the error of human operation.
  • the processing module transmits the display image to the display module for real-time display for the user to view.
  • the processing module transmits the images at different time points and images before and after the cancer thermochemotherapy to the storage module for storage.
  • the storage module transmits the stored image information to the comparison module for comparison, and the comparison module compares the images of different time electrics.
  • the module transmits the difference to the display module.
  • it is convenient for the user to view.
  • different time or different images before and after chemotherapy it indicates that the chemotherapy is effective or the lesion has metastasized.
  • different images are displayed in time and the user is prompted by the prompting module, so as to timely notify the user that the chemotherapy is effective or the lesion has some The effect of the transfer, to avoid artificial neglect has serious consequences.
  • the display module can select a three-dimensional image display device, which is convenient and intuitive for the user to view.
  • the nano-carbon when the nano-carbon suspension is injected around the cancer cell disease, the nano-carbon absorbs the infrared light by heating the infrared light when the corresponding software application is applied and the infrared emission module in the cancer thermal chemotherapeutic device is used to emit infrared rays.
  • the infrared radiation detection is detected by the detection module, and converted into an electrical signal and transmitted to the data acquisition module.
  • the data acquisition module transmits the collected data to the data acquisition module, and the data acquisition module processes the data accordingly, and obtains corresponding display. image. After obtaining information such as the number, distribution and orientation of lymph nodes, the high-power infrared emission module is used to warm the surrounding area of the lesion.
  • the nano-carbon is more capable of converting infrared rays into heat than other normal tissues of the human body, that is, after heating, after entering the draining lymph node.
  • the temperature of the nano-carbon can be warmed up faster than other normal tissues of the body. With this property, the lymph nodes of the lesion can be subjected to thermochemotherapy.
  • the temperature detection model can be used to detect the lymph nodes of the lesion and other normal tissues of the human body to ensure the killing. Cancer cells do not destroy other normal tissues of the human body.
  • the infrared transmitting module and the high-power infrared transmitting module are respectively connected with the time control module to realize automatic control of the infrared transmitting module and the high-power infrared transmitting module, and the time control unit enables the infrared transmitting module and the high-power infrared transmitting module to be accurately controlled.
  • Launch time to avoid errors in human operation.
  • the storage module stores the corresponding images at different times and before and after the chemotherapy, and compares them through the comparison module. When comparing the images at different times or before and after the chemotherapy, the chemotherapy is effective or the lesions are transferred. At this time, different images are displayed in time and the user is prompted by the prompting module, so as to timely notify the user that the chemotherapy is effective or the lesion has a metastasis effect, and avoiding the human neglect and causing serious consequences.

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Abstract

提供纳米炭混悬注射剂的新用途，具体涉及其用于制备配合近红外光（Near Infrared, NIR）使用的癌症诊断试剂及热疗试剂的药物中的应用；以及可与纳米炭混悬注射剂配合使用的纳米炭淋巴成像仪及癌热化疗仪。

Description

纳米炭混悬注射剂的新用途 技术领域
本发明涉及医药领域及其医药设备领域，涉及纳米炭混悬注射剂的新用途，具体涉及其用于制备配合近红外光(Near Infrared，NIR)使用的癌症诊断试剂及热疗试剂的药物中的应用；以及可与纳米炭混悬注射剂配合使用的纳米炭淋巴成像仪及癌热化疗仪。
背景技术
中国专利申请CN 1458185A，专利号：ZL02113731.5，发明名称：一种纳米炭混悬组合物的制备方法，公开了一种用于示踪恶性肿瘤的区域引流淋巴结的纳米炭混悬液的制备方法。该纳米炭混悬注射剂是目前应用较广的示踪恶性肿瘤引流淋巴结走向和分布的淋巴示踪剂，利用靶向性特点临床应用于诊断过程，即在手术中观察被染色的癌细胞组织及被浸染淋巴组织，由此判断癌细胞转移程度，有助于手术中完全切除癌细胞浸润组织，但是这种治疗方法也存在一些缺陷，如产生手术创口，愈合时间更长，给病人身体和精神上带来了极大的痛苦，同时手术治疗的费用较高，也会给患者家庭带来沉重的经济负担。因此，亟需开发一些创伤小，费用低，周期短，效果更好，毒副作用更低的肿瘤治疗方法。
光热治疗是近期发展起来的一类新型肿瘤治疗方法，由于创伤小、治疗效果明显，毒副作用更低，因此有极大的应用前景。在热疗试剂的开发过程中，碳纳米管、石墨烯、碳量子点、富勒烯是目前研究中的热点方向。这些材料中碳原子以SP2杂化形成共价键，并向周围延伸，形成蜂窝状六元环结构，环上π电子富集，形成离域大π键，因此SP2杂化赋予这些碳材料很多特殊性质，其中包括可以吸收NIR光。这些碳材料在吸收NIR后可以迅速将光能转化为热量，杀死肿瘤细胞，因此是理想的热疗潜在候选材料。经过长时间的科研数据积累，热疗试剂的开发取得了巨大的进步，其中有效提高热转化效率，表面修饰提高靶向性、毒性研究都取得了一定进展，但是在研究过程中也存在很多问题，限制了临床应用，主要存在以下缺陷：
(1)制备工艺控制难度大。碳纳米管、石墨烯、富勒烯的粗品杂质较多，在体内可能会会产生毒副反应，亲水性差，不利于在水中分散，因此需要精制和表面修饰。精制过程主要除去杂质，提高纯度，降低杂质产生毒副作用的风险。表面修饰主要是对碳的表面基团修饰，有利于在水中分散，同时提高热疗过程对NIR的转化效率。但是在试剂开发过程中发现，这些碳材料是一定粒径范围的混合物，在精制和表面修饰过程中很难控制批次间的一致性，导致批次间产品性质有差异，影响综合评价，阻碍了后期试验开展。
(2)颗粒形状和大小难以控制。上述材料中，碳纳米管为管状结构，在制备过程两个端头需要钝化处理，但通常情况可能处理不彻底，还存在部分如同针尖一样的端头，在给药后，这些锋利的端头很容易刺破血管壁，然后进入细胞核，存在潜在的遗传毒性。
(3)靶向性较差，精准度不够。局部给药后，碳纳米管、石墨烯、碳量子点、富勒烯的靶向性不好，它们在肿瘤周围富集的同时，部分会弥散到正常组织周围。在热疗中，弥散在正常组织周围的碳也会发热，导致正常组织灼伤。
(4)成本较高。由于制备工艺复杂，涉及制备、精制、化学修饰等步骤，成本较高，限 制其规模化生产和临床应用。
在上述应用背景下，热疗制剂的应用一直仅限于前期探索阶段，未出现一种可安全稳定可控的进入临床应用阶段的试剂，可安全有效的供患者使用。本申请的发明人以下将提供的技术方案正好解决了这一应用困境。
发明内容
本发明所解决的第一个技术问题是提供纳米炭混悬注射剂的新用途，具体涉及其用于制备配合近红外光(Near Infrared，NIR)使用的癌症诊断试剂及热疗试剂的药物中的应用。
在纳米炭混悬注射剂的诊断应用背景下，发明人首次提出利用纳米炭混悬注射剂的示踪恶性肿瘤引流淋巴结走向和分布(淋巴趋向性)的特性，采用近红外光加热诊断组织，由于纳米炭混悬注射剂能够有效吸收红外射线转化为热量，由此使得癌细胞与正常细胞产生较大的温差，正常细胞温度不发生变化约在37℃左右；而有纳米炭的癌组织在吸收热量后温度达到53～55℃，通过热成像仪区分癌细胞与正常细胞，以及判断癌细胞的分布、转移情况，为公众提供了一种利用纳米炭混悬注射剂无创诊断癌细胞及恶性肿瘤引流淋巴结走向和分布的新方法。
更进一步的，发明人还提供了利用纳米炭混悬注射剂的淋巴示踪的靶向性，以及纳米炭混悬注射剂能够有效吸收红外射线转化为热量的特性，采用近红外加热诊断为含癌细胞的组织及部位，使得癌细胞温度急速上升，大致处于50-56℃被高温杀死，而正常细胞在短时间内处于人体能够接受的水平，实现恶性肿瘤原发部位及其引流淋巴转移热疗的目的。
其中，所采用的近红外光的波长为780-2600nm，优选波长为785-1400nm；能量为0.5-7680J/cm2，优选能量为60-4590J/cm2。
本发明中所述纳米炭混悬注射剂是按照中国专利申请CN 1458185A(专利号：ZL02113731.5)发明名称为一种纳米炭混悬组合物的制备方法的发明专利所述方法制备。具体地，所述纳米炭混悬注射剂是由纳米炭，PVP，生理盐水、pH调节剂组成，其中纳米炭的粒径为50-250nm。优选粒径范围为100-150nm。
每1000ml纳米炭混悬注射剂中，含纳米炭2.5-200g、聚乙烯比咯烷酮(PVP)2-200g、pH值调节剂调pH值至6.5-8.0，余量为生理盐水。优选，每1000ml纳米炭混悬注射剂中，含纳米炭50g、聚乙烯比咯烷酮(PVP)20g、pH值调节剂调pH值至7.0，余量为生理盐水。
其中，所述纳米炭是由炭黑经过有机溶剂出去脂溶性杂质，干燥除去有机物残留；酸洗、碱洗除去无机杂质；水洗除去酸、碱和无机物残留干燥获得。
所述pH调节剂可以是任何可以调节pH的化学物质，包括枸橼酸钠、枸橼酸、氢氧化钠、盐酸、醋酸、酒石酸、乳酸。最适宜的pH调节剂是枸橼酸钠。
本发明所述纳米炭混悬注射剂的制备方法之一：称取聚乙烯吡咯烷酮(优选PVP K30)50g，溶解于300ml生理盐水中；再称取纳米炭20g，搅拌下加入聚乙烯吡咯烷酮溶液中，再继续加入生理盐水至1000ml；加入振动磨中；室温下振动分散5分钟；用1mol/L枸橼酸钠调节pH至6.5-8.0。
本发明所述纳米炭混悬注射剂的制备方法之一：称取聚乙烯吡咯烷酮K30 50g，溶解于 300ml生理盐水中；再称取纳米炭20g，搅拌下加入聚乙烯吡咯烷酮溶液中，再继续加入生理盐水至1000ml；加入球磨中；室温下球磨分散96小时；用1mol/L枸橼酸钠调节pH至6.5-8.0。
进一步的，为了提高热疗的治疗效果，还可以将纳米炭混悬注射剂与抗癌药混合使用。
具体的，可以配合使用的抗癌药有阿霉素，表阿霉素，顺铂，紫杉醇，5-氟尿嘧啶(5-FU)。
还可以由此制备成新的抗癌药物组合物，其特征在于：它含有下述重量配比的组分：抗癌药0.0312５－32份，纳米炭0.5-400份；
优选配比范围：抗癌药0.125-8份，纳米炭1-100份；
最优配比：抗癌药1份，纳米炭5份。
亦可用浓度(μg/ml)比表示：抗癌药∶纳米炭＝0.03125-32∶0.5-400；
优选配比范围：抗癌药∶纳米炭＝0.125-8∶1-100；
最优配比：抗癌药∶纳米炭＝1∶5。
所述抗癌药为阿霉素，表阿霉素，顺铂，紫杉醇，5-氟尿嘧啶(5-FU)；优选阿霉素。
通过热疗细胞试验表明：细胞加纳米炭后无近红外光照射组和细胞不加纳米炭用近红外光照射组对细胞基本无影响；温度为35℃和37℃时对细胞无影响，随着温度的上升，对细胞的抑制率也逐渐上升，当温度达到53℃时，对细胞的抑制率达到90％以上。温度为42℃时，5种药物(阿霉素，表阿霉素，顺铂，紫杉醇，5-FU)加入纳米炭用近红外光照射后抑制率大大提高。加入纳米炭照射使温度达到42℃时，1μg/ml阿霉素的抑制率与4μg/ml阿霉素的抑制率相当。
本发明所解决的第二个技术问题是提供一种纳米炭淋巴成像仪，使用时，增加对应的软件应用，可以达到有效、方便、准确的检测出淋巴结数量、分布及走向等信息的效果，用于配合本发明采用的纳米炭混悬注射剂实现制备配合近红外光使用的癌症诊断试剂的药物中的应用。
本发明纳米炭淋巴成像仪，包括探测模块，还包括红外发射模块、时间控制模块、数据采集模块、处理模块、存储模块、比较模块及显示模块，所述时间控制模块、数据采集模块、存储模块及显示模块分别与处理模块连接，所述探测模块与数据采集模块连接，红外发射模块与时间控制模块连接，比较模块分别与存储模块及显示模块连接。
具体的，所述红外发射模块为红外发光二极管阵列。
具体的，所述纳米炭淋巴成像仪还包括提示模块，所述提示模块与比较模块连接。
进一步的，所述提示模块为LED灯。
具体的，所述探测模块为红外接收器。
具体的，所述显示模块为三维图像显示装置。
本发明纳米炭淋巴成像仪的有益效果是，当将纳米炭混悬液注射到癌细胞病症周围后，通过增加对应的软件应用及利用纳米炭淋巴成像仪中的红外发射模块发射红外线，纳米炭吸收红外线升温当其和周围人体组织形成温差时通过探测模块行红外辐射探测，并将其转换为电信号传输给数据采集模块，数据采集模块将采集的数据传输给数据采集模块，数据采集模块对数据进行相应处理，得到相应显示图像，存储模块对显示图像进行对应时间的 存储，并通过比较模块进行比较，当比较出不同时间的图像有不同点时，说明病灶有所转移，此时，及时显示出不同图像且通过提示模块提示用户，从而达到及时通知用户病灶有所转移的效果，避免人为的忽略造成严重后果。同时，处理模块通过时间控制单元与红外发射模块连接，实现了红外发射模块的自动控制，且时间控制单元使得红外发射模块能够精准的控制红外发射时间，避免人为操作的误差。
本发明所解决的第三个技术问题是提供一种癌热化疗仪，使用时，增加对应的软件应用，可以有效、方便、准确的检测出淋巴结数量、分布及走向等信息，得到以上信息后，可以有效达到的对淋巴结进行精准的癌热化疗的效果。，用于配合本发明采用的纳米炭混悬注射剂实现制备配合近红外光使用的癌症热疗试剂的药物中的应用。
本发明癌热化疗仪，包括探测模块、红外发射模块、大功率红外发射模块、温度检测模块、时间控制模块、数据采集模块、处理模块、存储模块、比较模块及显示模块，所述温度检测模块、时间控制模块、数据采集模块、存储模块及显示模块分别与处理模块连接，所述探测模块与数据采集模块连接，红外发射模块及大功率红外发射模块分别与时间控制模块连接，比较模块分别与存储模块及显示模块连接。
具体的，所述红外发射模块为红外发光二极管阵列。
具体的，所述癌热化疗仪还包括提示模块，所述提示模块与比较模块连接。
进一步的，所述提示模块为LED灯。
具体的，所述探测模块为红外接收器。
具体的，所述显示模块为三维图像显示装置。
本发明癌热化疗仪的有益效果是，当将纳米炭混悬液注射到癌细胞病症周围后，通过增加对应的软件应用及利用癌热化疗仪中的红外发射模块发射红外线，纳米炭吸收红外线升温当其和周围人体组织形成温差时通过探测模块进行红外辐射探测，并将其转换为电信号传输给数据采集模块，数据采集模块将采集的数据传输给数据采集模块，数据采集模块对数据进行相应处理，得到相应显示图像。得到淋巴结数量、分布及走向等信息后，利用大功率红外发射模块对病灶周围进行加温，纳米炭比人体其他正常组织更能红外线转化为热量，也就是说，加温后，进入引流淋巴结后的纳米炭的温度能够比身体其他正常组织升温快，利用这个性质可以对病灶淋巴结进行热化疗，热化疗的同时利用温度检测模对病灶淋巴结及人体其他正常组织进行实时温度检测，保证在杀死癌细胞的同时不破坏人体其他正常组织。同时，红外发射模块及大功率红外发射模块分别与时间控制模块连接，实现红外发射模块及大功率红外发射模块的自动控制，且时间控制单元使得红外发射模块及大功率红外发射模块能够精准的控制发射时间，避免人为操作的误差。并且，存储模块对不同时间及化疗前后的显示图像进行对应时间的存储，并通过比较模块进行比较，当比较出不同时间或化疗前后的图像有不同点时，说明化疗有效或病灶有所转移，此时，及时显示出不同图像且通过提示模块提示用户，从而达到及时通知用户化疗有效或病灶有所转移的效果，避免人为的忽略造成严重后果。
附图说明
图1为不同治疗组的肿瘤体积生长曲线。
图2为不同治疗组裸鼠的存活率。
图3为不同治疗组对转移性淋巴结的生长抑制效果。
图4为纳米炭淋巴成像仪的实施例1结构图。
图5为纳米炭淋巴成像仪的实施例2结构图。
图6为癌热化疗仪的实施例3结构图。
图7为癌热化疗仪的实施例4结构图。
具体实施方式
以下通过实施例形式的具体实施方式，对本发明的上述内容再作进一步的详细说明，说明但不限制本发明。
本发明的使用原理是：
1.纳米炭能够有效将NIR转化为热量。
2.与其他波长的光相比NIR通过生物组织时衰减较小。
3.通过组织的能力是将其用来治疗非表浅肿瘤的一个条件。
4.纳米炭在NIR中进入激发状态，释放振动能量并转化成热量可以导致细胞死亡，纳米炭有广泛的电磁吸收范围，覆盖NIR I和II窗口的整个波长，而该波长对生物组织是光穿透窗户。也是雷达的波长和微波的波长。
本发明纳米炭混悬注射剂配合近红外光(Near Infrared，NIR)作为癌症诊断试剂使用的实施方式是将纳米炭混悬液注射到癌病灶周围，很快(约小于10分钟)进入引流淋巴结，纳米炭吸收红外线后升温，和周围正常组织细胞形成可检测的温差，通过热成像仪就可以形象的反应出被纳米炭示踪的淋巴结数量、分布、走向等重要临床信息。
本发明纳米炭混悬注射剂配合近红外光(Near Infrared，NIR)作为热疗试剂使用的实施方式是将纳米炭混悬液注射到癌病灶周围，很快(约小于10分钟)进入引流淋巴结及癌症细胞，纳米炭吸收红外线后升温，使得癌细胞温度急速上升，大致处于50-56℃被高温杀死，而正常细胞在短时间内处于人体能够接受的水平，实现恶性肿瘤原发部位及其引流淋巴转移热疗的目的。
具体的，可用于乳腺癌，脑癌，宫颈癌，肾癌，肝癌，前列腺癌，口腔癌，淋巴瘤，神经内分泌癌，皮肤癌等癌症的诊断和治疗。
一、细胞热疗、热化疗实验
(一)试验材料：
1)细胞株：
人肝癌细胞系HepG2细胞、人宫颈癌细胞系HeLa细胞、人乳腺癌细胞系MCF-7细胞。
2)细胞培养基：
细胞用DMEM培养基、胎牛血清(FCS)、细胞消化液胰酶、青霉素链霉素混合液、磷酸盐缓冲液(PBS，pH 7.4)。
3)实验药品及主要仪器设备：
纳米炭混悬注射液、注射用盐酸多柔比星(即阿霉素，阿霉素)、注射用盐酸表柔比星(即表阿霉素)、顺铂注射液、紫杉醇注射液、注射用5-氟尿嘧啶(5-FU)。
医用超声波清洗器、离心机、高速离心机、鼓风干燥箱、恒温水浴锅、倒置荧光显微镜、全自动定量绘图酶标仪、生物光学显微镜、恒温培养箱、纯水仪、高压灭菌锅、超净工作台、pH计、漩涡混合器、恒温摇床、1064nm激光发射器、红外温度计。
(二)实验方法：
1)阿霉素对3种细胞的抑制率：收集对数期生长的细胞，调整细胞悬液浓度，96孔板中每孔加入100μL，铺板使待测细胞密度为1×103～104个/孔(边缘孔用无菌PBS填充)。5％CO2，37℃孵育24h，加入浓度梯度的阿霉素，然后在5％CO2，37℃条件下孵育48h。每孔加入10μLCCK8溶液，继续培养2h。在酶标仪OD＝450nm处测量各孔的吸光值。同时设阴性对照组。
2)热疗：96孔板中细胞加入纳米炭混悬注射液，使纳米炭的最终浓度为25μg/ml，使用近红外光照射细胞一段时间(1～10min)，并测量其温度，使温度分别为35℃、37℃、42℃、45℃、50℃、53℃，继续培养24h后，加入CCK8试剂孵育一定时间后测定其OD值，计算不同温度对细胞的抑制率。设置细胞加纳米炭后无近红外光照射、细胞不加纳米炭用近红外光照射的对照组。
3)热化疗：96孔板中细胞加入不同药物(纳米炭混悬注射液吸附不同的药物，浓度比为抗癌药∶纳米炭＝1∶5)后，用近红外光照射一定的时间(2～8min)，使温度分别为37℃、42℃、45℃，继续培养24h后，加入CCK8试剂孵育一定时间后测定其OD值，计算各种药物对细胞的抑制率。
(三)实验结果：
表1阿霉素对3种细胞的抑制率
Figure PCTCN2015000250-appb-000001
表2纳米炭热疗结果
Figure PCTCN2015000250-appb-000002
表3纳米炭热化疗结果(盐酸多柔比星)
Figure PCTCN2015000250-appb-000003
备注：注射用盐酸多柔比星(即阿霉素，阿霉素)：均为1μg/ml
表4纳米炭热化疗结果(盐酸表柔比星)
Figure PCTCN2015000250-appb-000004
备注：注射用盐酸表柔比星(即表阿霉素)：均为1μg/ml
表5纳米炭热化疗结果(顺铂注射液)
Figure PCTCN2015000250-appb-000005
备注：顺铂注射液：均为5μg/ml
表6纳米炭热化疗结果(紫杉醇注射液)
Figure PCTCN2015000250-appb-000006
表7纳米炭热化疗结果(5-氟尿嘧啶)
Figure PCTCN2015000250-appb-000007
备注：注射用5-氟尿嘧啶(5-FU)；均为5μg/ml
(四)实验小结：
细胞加纳米炭后无近红外光照射组和细胞不加纳米炭用近红外光照射组对细胞基本无影响；温度为35℃和37℃时对细胞无影响，随着温度的上升，对细胞的抑制率也逐渐上升，当温度达到53℃时，对细胞的抑制率达到90％以上。温度为42℃时，5种药物加入纳米炭用近红外光照射后抑制率大大提高。加入纳米炭照射使温度达到42℃时，1μg/ml阿霉素的抑制率与4μg/ml阿霉素的抑制率相当。
二、动物热疗实验
(一)实验材料：
1)细胞株：
人肝癌细胞系SMMC7721细胞、鼠源性肝癌H22细胞。
2)细胞培养基：
细胞用DMEM培养基、胎牛血清(FCS)、细胞消化液胰酶、青霉素链霉素混合液、磷酸盐缓冲液(PBS，pH 7.4)。
3)实验动物：
BaIB/c-nu小鼠，雌性，4～6周龄，体重20±2g。实验过程中自由饮水及进食。每日光照12h，小鼠5只/笼，采用独立送风隔离笼具饲养。
清洁级近交系昆明小鼠，雌性，6-7周龄，体重20±2g。实验过程中自由饮水及进食。每日光照12h，小鼠(5只/笼)笼均采用中央换气系统通气。
4)实验药品及主要仪器设备
纳米炭混悬注射液。
医用超声波清洗器、离心机、高速离心机、鼓风干燥箱、恒温水浴锅、倒置荧光显微镜、生物光学显微镜、恒温培养箱、纯水仪、高压灭菌锅、超净工作台、1064nm激光发射器、红外温度计。
(二)实验方法：
1)收集对数生长期的SMMC7721细胞，调整细胞悬液浓度为1×107个细胞/mL，将细胞接种于裸鼠左下腋窝皮下0.1mL/只(约含细胞数1×106个)，待接种好的小鼠瘤体积平均达100mm3时将荷瘤鼠随机分组，分别为纳米炭激光照射组、纳米炭组、激光照射组、阴性对照组(无纳米炭、无激光)，每组10只裸鼠。瘤内注射纳米炭后10min，用1064nm激光器照射肿瘤5min，激光功率为3W/cm2。照射期间记录肿瘤部位上升的温度。记录每天的肿瘤体积变化及裸鼠生存率，观察到60天，体积计算公式为：体积＝(长度×宽度2)/2。照射后2天，每组取2只裸鼠肿瘤及周围正常组织做病理组织学观察。
2)抽取H22荷瘤小鼠乳白色浓稠腹水，调整细胞数为2×107个细胞/mL，在昆明小鼠左后肢足垫皮下接种0.05mL细胞悬液，得到癌淋巴结转移小鼠模型。当肿瘤直径达6～8mm、既无溃疡也无坏死时治疗小鼠。将小鼠随机分成4组，每组10只，分别为纳米炭激光照射组、纳米炭组、激光照射组、阴性对照组(无纳米炭、无激光)。小鼠左后肢足垫皮下注射0.05ml纳米炭溶液10min后，用1064nm激光器照射小鼠左后肢腘窝淋巴结处的去毛皮肤5min，激光功率为3W/cm2。照射后2周，处死小鼠并收集腘淋巴结。腘淋巴结称重并测量体积，体积计算公式为：体积＝(长度×宽度2)/2。并取腘淋巴结及其周围正常组织做病理学检查。
(三)实验结果：
1)激光照射后检测肿瘤表面的温度。激光照射组温度上升平均为7.2±0.8℃，纳米炭激光照射组温度上升平均为19.1±1.5℃。与激光照射组相比，纳米炭激光照射组具有显著的意义。由于有裸鼠死亡，只观察了10天的肿瘤体积。纳米炭组、激光照射组肿瘤持续生长，纳米炭激光照射组肿瘤消失(见图1)。到45天时，除纳米炭激光照射组外，其余3组裸鼠全部死亡(见表8、图2)。组织病理学检查显示，纳米炭组及激光照射组与对照组相似，肿瘤细胞有明显的核异形及分化，纳米炭激光照射组整个肿瘤凝固性坏死。纳米炭组及纳米炭激光照射组肿瘤组织观察到黑色纳米颗粒。3个治疗组周围正常组织无明显 损伤。
2)使用淋巴结转移模型，我们评估了纳米炭淋巴靶向热疗的抗癌活性。纳米炭组及激光照射组没有减小转移性淋巴结的体积，纳米炭激光照射组明显减小淋巴结的体积。其结果与淋巴结称重结果一致(见图3)。淋巴结HE染色显示，纳米炭组及激光照射组与对照组相似，肿瘤细胞有明显的核异形，存在不同程度的细胞坏死。纳米炭激光照射组肿瘤细胞凝固性坏死。纳米炭组及纳米炭激光照射组淋巴结观察到黑色纳米颗粒。3个治疗组周围正常组织无明显损伤。
表8不同治疗组裸鼠的生存率
Figure PCTCN2015000250-appb-000008
(四)实验小结
纳米炭溶液瘤内注射后用激光照射，温度上升明显，可以完全治愈肿瘤，肿瘤复发率较低，存活率高，表现出很好的抗癌活性。利用纳米炭的热疗特性和淋巴靶向性，可将纳米炭用于淋巴靶向热疗。实验中建立的转移性淋巴结热疗实验也表明，纳米炭进入淋巴结后用激光照射，可以减小转移淋巴结的重量和体积，肿瘤细胞凝固性坏死。
而且，发明人在应用过程中发现，小鼠腹腔注射纳米炭注射液后14天内，无死亡现象，说明纳米炭注射液无急性毒性，保障了临床用药安全。更重要的是，纳米炭混悬注射液作为淋巴示踪剂已上市近10年，临床使用的患者达十几万例，至今未见不良反应的报道，说明纳米炭混悬注射液局部应用无毒性，进一步保障了临床用药安全。
下面结合附图及实施例详细描述的技术方案解释及说明纳米炭淋巴成像仪和癌热化疗仪的有益效果：
20世纪末期至21世纪，人类疾病面临重大变化，主要杀手从感染性疾病变为癌症。在医学领域中，癌细胞淋巴转移是指恶性肿瘤细胞脱离其原发部分，通过直接蔓延，淋巴道，血道和种植等途径扩散到身体的其他部位，甚至在多个器官内继续增殖生长，形成同样性质的肿瘤。在中晚期癌症病人常发生淋巴转移。淋巴道转移是影响恶性肿瘤预后的重要因素之一，许多肿瘤患者的命运常常不是由原发灶所决定的。因而，有效地对肿瘤引流区域淋巴结进行清术，是提高病人生存质量、延长病人寿命的重要手段。传统技术上，通常采用切开手术方式去除淋巴，经过化验，以判断癌细胞是否扩散。这种方式并不方便，且给病人带来了极大的痛苦。目前为止，还没有专门的跟踪仪器能够准确的，有效的，方便的观测出淋巴结数量、分布及走向等信息。基于上述技术背景，本发明提供的纳米炭淋巴成像仪和癌热化疗仪能够有效配合纳米炭混悬注射剂实现诊断和治疗的应用。
针对现有技术中，还没有一种专门的跟踪仪器能够准确的，有效的，方便的观测出淋巴结数量、分布及走向等信息的问题，本发明提供了一种纳米炭淋巴成像仪，包括探测模块，还包括红外发射模块、时间控制模块、数据采集模块、处理模块、存储模块、比较模 块及显示模块，所述时间控制模块、数据采集模块、存储模块及显示模块分别与处理模块连接，所述探测模块与数据采集模块连接，红外发射模块与时间控制模块连接，比较模块分别与存储模块及显示模块连接。当将纳米炭混悬液注射到癌细胞病症周围后，通过增加对应的软件应用及利用纳米炭淋巴成像仪中的红外发射模块发射红外线，纳米炭吸收红外线升温当其和周围人体组织形成温差时通过探测模块行红外辐射探测，并将其转换为电信号传输给数据采集模块，数据采集模块将采集的数据传输给处理模块，处理模块对数据进行相应处理，得到相应显示图像，存储模块对显示图像进行对应时间的存储，并通过比较模块进行比较，当比较出不同时间的图像有不同点时，说明病灶有所转移，此时，及时显示出不同图像且通过提示模块提示用户，从而达到及时通知用户病灶有所转移的效果，避免人为的忽略造成严重后果。同时，处理模块通过时间控制单元与红外发射模块连接，实现了红外发射模块的自动控制，且时间控制单元使得红外发射模块能够精准的控制红外发射时间，避免人为操作的误差。
实施例1
本例的纳米炭淋巴成像仪，如图4所示，包括探测模块，还包括红外发射模块、时间控制模块、数据采集模块、处理模块、存储模块、比较模块及显示模块，所述时间控制模块、数据采集模块、存储模块及显示模块分别与处理模块连接，所述探测模块与数据采集模软连接，红外发射模块与时间控制模块连接，比较模块分别与存储模块及显示模块连接。
炭黑(Carbonblack，CB)生物相容性好，无毒副作用，而且具有巨大的比表面积，且可以靶向地进入淋巴结利用这一特点。需要对淋巴结进行跟踪时，向癌细胞病症周围注射纳米炭混悬液，纳米炭混悬液进入引流淋巴结后，利用纳米炭淋巴成像仪中的红外发射模块发射红外线对人体进行照射。使用时，需增加对应的软件应用，由于本例的纳米炭淋巴成像仪中的处理模块通过时间控制模块与红外发射模块连接。使用该纳米炭淋巴成像仪时，可以实现红外发射模块的自动控制，用户可以根据需要自行设置所需照射时间，从而能够精准的控制红外发射模块的控制红外发射时间，避免人为操作的误差。优选的，红外发射模块为红外发光二极管阵列。能够实现不同面积、不同位置的发射需求。
当红外发光二极管阵列发射红外确定的时间后，病患体内的纳米炭吸收红外线升温至和周围人体组织形成温差。此时，通过探测模块行红外辐射探测，并将探测信息转换为电信号传输给数据采集模块，数据采集模块将采集的数据传输给处理模块，处理模块对数据进行相应处理，得到相应显示图像。
一方面，处理模块将显示图像传输给显示模块进行实时显示，以便用户进行查看。另一方面，处理模块将不同时间点的图像传输给存储模块进行存储。存储模块将存储的图像信息传输给比较模块进行比较，比较模块对不同时间电的图像进行比较，当比较出不同时间点的图像差异时，传输给显示模块，将差异显示给用户，方便用户查看。
优选的，显示模块可选用三维图像显示装置，可使用户查看起来更加方便，直观。
实施例2
本例的纳米炭淋巴成像仪在实施例1的基础上增加了提示模块。所述提示模块与比较模块连接。即本例的纳米炭淋巴成像仪，如图5所示，包括探测模块，还包括红外发射模 块、时间控制模块、数据采集模块、处理模块、存储模块、比较模块、提示模块及显示模块，所述时间控制模块、数据采集模块、存储模块及显示模块分别与处理模块连接，所述探测模块与数据采集模块连接，红外发射模块与时间控制模块连接，比较模块分别与存储模块、提示模块及显示模块连接。提示模块可以通过LED显示提示，也可以通过声响等方式提示用户。
炭黑(Carbonblack，CB)生物相容性好，无毒副作用，而且具有巨大的比表面积，且可以靶向地进入淋巴结利用这一特点。需要对淋巴结进行跟踪时，向癌细胞病症周围注射纳米炭混悬液，纳米炭混悬液进入引流淋巴结后，利用纳米炭淋巴成像仪中的红外发射模块发射红外线对人体进行照射。使用时，需增加对应的软件应用，由于本例的纳米炭淋巴成像仪中的处理模块通过时间控制模块与红外发射模块连接。使用该纳米炭淋巴成像仪时，可以实现红外发射模块的自动控制，用户可以根据需要自行设置所需照射时间，从而能够精准的控制红外发射模块的控制红外发射时间，避免人为操作的误差。优选的，红外发射模块为红外发光二极管阵列。能够实现不同面积、不同位置的发射需求。
当红外发光二极管阵列发射红外确定的时间后，病患体内的纳米炭吸收红外线升温至和周围人体组织形成温差。此时，通过探测模块行红外辐射探测，并将探测信息转换为电信号传输给数据采集模块，数据采集模块将采集的数据传输给处理模块，处理模块对数据进行相应处理，得到相应显示图像。
一方面，处理模块将显示图像传输给显示模块进行实时显示，以便用户进行查看。另一方面，处理模块将不同时间点的图像传输给存储模块进行存储。存储模块将存储的图像信息传输给比较模块进行比较，比较模块对不同时间电的图像进行比较，当比较出不同时间点的图像差异时，传输给显示模块，将差异显示给用户，方便用户查看。同时，当比较模块比较出不同时间点得图像差异时，说明病灶有所转移，系统通过提示模块提示用户查看不同点。通过及时显示出不同图像且通过提示模块提示用户，从而达到及时通知用户病灶有所转移的效果，避免人为的忽略造成严重后果。
优选的，显示模块可选用三维图像显示装置，可使用户查看起来更加方便，直观。
综上所述，当将纳米炭混悬液注射到癌细胞病症周围后，通过增加对应的软件应用及利用纳米炭淋巴成像仪中的红外发射模块发射红外线，纳米炭吸收红外线升温当其和周围人体组织形成温差时通过探测模块行红外辐射探测，并将其转换为电信号传输给数据采集模块，数据采集模块将采集的数据传输给处理模块，处理模块对数据进行相应处理，得到相应显示图像，存储模块对显示图像进行对应时间的存储，并通过比较模块进行比较，当比较出不同时间的图像有不同点时，说明病灶有所转移，此时，及时显示出不同图像且通过提示模块提示用户，从而达到及时通知用户病灶有所转移的效果，避免人为的忽略造成严重后果。同时，处理模块通过时间控制单元与红外发射模块连接，实现了红外发射模块的自动控制，且时间控制单元使得红外发射模块能够精准的控制红外发射时间，避免人为操作的误差。
针对现有技术中，切开手术方式去除淋巴或以放射性化疗等治疗方式给病人带来了极大的痛苦，且不能精准的只对病灶有效，这些方式普遍的在杀死癌细胞的同时，杀死了人 体其他正常组织的问题，本发明提供了一种癌热化疗仪，包括探测模块、红外发射模块、大功率红外发射模块、温度检测模块、时间控制模块、数据采集模块、处理模块、存储模块、比较模块及显示模块，所述温度检测模块、时间控制模块、数据采集模块、存储模块及显示模块分别与处理模块连接，所述探测模块与数据采集模块连接，红外发射模块及大功率红外发射模块分别与时间控制模块连接，比较模块分别与存储模块及显示模块连接。当将纳米炭混悬液注射到癌细胞病症周围后，通过增加对应的软件应用及利用癌热化疗仪中的红外发射模块发射红外线，纳米炭吸收红外线升温当其和周围人体组织形成温差时通过探测模块行红外辐射探测，并将其转换为电信号传输给数据采集模块，数据采集模块将采集的数据传输给数据采集模块，数据采集模块对数据进行相应处理，得到相应显示图像。得到淋巴结数量、分布及走向等信息后，利用大功率红外发射模块对病灶周围进行加温，纳米炭比人体其他正常组织更能红外线转化为热量，也就是说，加温后，进入引流淋巴结后的纳米炭的温度能够比身体其他正常组织升温快，利用这个性质可以对病灶淋巴结进行热化疗，热化疗的同时利用温度检测模对病灶淋巴结及人体其他正常组织进行实时温度检测，保证在杀死癌细胞的同时不破坏人体其他正常组织。同时，红外发射模块及大功率红外发射模块分别与时间控制模块连接，实现红外发射模块及大功率红外发射模块的自动控制，且时间控制单元使得红外发射模块及大功率红外发射模块能够精准的控制发射时间，避免人为操作的误差。并且，存储模块对不同时间及化疗前后的显示图像进行对应时间的存储，并通过比较模块进行比较，当比较出不同时间或化疗前后的图像有不同点时，说明化疗有效或病灶有所转移，此时，及时显示出不同图像且通过提示模块提示用户，从而达到及时通知用户化疗有效或病灶有所转移的效果，避免人为的忽略造成严重后果。
实施例3
本例的癌热化疗仪，如图6所示，包括探测模块、红外发射模块、大功率红外发射模块、温度检测模块、时间控制模块、数据采集模块、处理模块、存储模块、比较模块及显示模块，所述温度检测模块、时间控制模块、数据采集模块、存储模块及显示模块分别与处理模块连接，所述探测模块与数据采集模块连接，红外发射模块及大功率红外发射模块分别与时间控制模块连接，比较模块分别与存储模块及显示模块连接。
炭黑(Carbonblack，CB)生物相容性好，无毒副作用，而且具有巨大的比表面积，且可以靶向地进入淋巴结利用这一特点。需要对淋巴结进行跟踪时，向癌细胞病症周围注射纳米炭混悬液，纳米炭混悬液进入引流淋巴结后，利用癌热化疗仪中的红外发射模块发射红外线对人体进行照射。使用时，需增加对应的软件应用，由于本例的癌热化疗仪中的处理模块通过时间控制模块与红外发射模块连接。使用该癌热化疗仪时，可以实现红外发射模块的自动控制，用户可以根据需要自行设置所需照射时间，从而能够精准的控制红外发射模块的控制红外发射时间，避免人为操作的误差。优选的，红外发射模块为红外发光二极管阵列。能够实现不同面积、不同位置的发射需求。
当红外发光二极管阵列发射红外确定的时间后，病患体内的纳米炭吸收红外线升温至和周围人体组织形成温差。此时，通过探测模块行红外辐射探测，并将探测信息转换为电信号传输给数据采集模块，数据采集模块将采集的数据传输给处理模块，处理模块对数据 进行相应处理，得到相应显示图像。
当根据显示图像得知病患体内的淋巴结数量、分布及走向等信息后，利用大功率红外发射模块对病灶周围进行加温，纳米炭比人体其他正常组织更能红外线转化为热量，也就是说，加温后，进入引流淋巴结后的纳米炭的温度能够比身体其他正常组织升温快，利用这个性质可以对病灶淋巴结进行热化疗，热化疗的同时利用温度检测模对病灶淋巴结及人体其他正常组织进行实时温度检测，保证在杀死癌细胞的同时不破坏人体其他正常组织。温度检测模块为红外接收装置，对病患进行红外辐射探测，可准确得知淋巴结及其他正常人体组织的温度状态，一旦人体正常组织达到39度，传输给处理模块，处理模块命令大功率红外发射模块停止工作，避免了人为操作的误差。同时，红外发射模块及大功率红外发射模块分别与时间控制模块连接，实现红外发射模块及大功率红外发射模块的自动控制，且时间控制单元使得红外发射模块及大功率红外发射模块能够精准的控制发射时间，也避免了人为操作的误差。
一方面，处理模块将显示图像传输给显示模块进行实时显示，以便用户进行查看。另一方面，处理模块将不同时间点的图像及癌热化疗前后的图像传输给存储模块进行存储。存储模块将存储的图像信息传输给比较模块进行比较，比较模块对不同时间电的图像进行比较，当比较出不同时间点的图像及癌热化疗前后的差异时，传输给显示模块，将差异显示给用户，方便用户查看。
优选的，显示模块可选用三维图像显示装置，可使用户查看起来更加方便，直观。
实施例4
本例的癌热化疗仪在实施例3的基础上增加了提示模块。所述提示模块与比较模块连接。即本例的癌热化疗仪，如图7所示，包括探测模块、红外发射模块、大功率红外发射模块、温度检测模块、时间控制模块、数据采集模块、处理模块、存储模块、比较模块及显示模块，所述温度检测模块、时间控制模块、数据采集模块、存储模块及显示模块分别与处理模块连接，所述探测模块与数据采集模块连接，红外发射模块及大功率红外发射模块分别与时间控制模块连接，比较模块分别与存储模块、提示模块及显示模块连接。提示模块可以通过LED显示提示，也可以通过声响等方式提示用户。
炭黑(Carbonblack，CB)生物相容性好，无毒副作用，而且具有巨大的比表面积，且可以靶向地进入淋巴结利用这一特点。需要对淋巴结进行跟踪时，向癌细胞病症周围注射纳米炭混悬液，纳米炭混悬液进入引流淋巴结后，利用癌热化疗仪中的红外发射模块发射红外线对人体进行照射。使用时，需增加对应的软件应用，由于本例的癌热化疗仪中的处理模块通过时间控制模块与红外发射模块连接。使用该癌热化疗仪时，可以实现红外发射模块的自动控制，用户可以根据需要自行设置所需照射时间，从而能够精准的控制红外发射模块的控制红外发射时间，避免人为操作的误差。优选的，红外发射模块为红外发光二极管阵列。能够实现不同面积、不同位置的发射需求。
当红外发光二极管阵列发射红外确定的时间后，病患体内的纳米炭吸收红外线升温至和周围人体组织形成温差。此时，通过探测模块行红外辐射探测，并将探测信息转换为电信号传输给数据采集模块，数据采集模块将采集的数据传输给处理模块，处理模块对数据 进行相应处理，得到相应显示图像。
当根据显示图像得知病患体内的淋巴结数量、分布及走向等信息后，利用大功率红外发射模块对病灶周围进行加温，纳米炭比人体其他正常组织更能红外线转化为热量，也就是说，加温后，进入引流淋巴结后的纳米炭的温度能够比身体其他正常组织升温快，利用这个性质可以对病灶淋巴结进行热化疗，热化疗的同时利用温度检测模对病灶淋巴结及人体其他正常组织进行实时温度检测，保证在杀死癌细胞的同时不破坏人体其他正常组织。温度检测模块为红外接收装置，对病患进行红外辐射探测，可准确得知淋巴结及其他正常人体组织的温度状态，一旦人体正常组织达到39度，传输给处理模块，处理模块命令大功率红外发射模块停止工作，避免了人为操作的误差。同时，红外发射模块及大功率红外发射模块分别与时间控制模块连接，实现红外发射模块及大功率红外发射模块的自动控制，且时间控制单元使得红外发射模块及大功率红外发射模块能够精准的控制发射时间，也避免了人为操作的误差。
一方面，处理模块将显示图像传输给显示模块进行实时显示，以便用户进行查看。另一方面，处理模块将不同时间点的图像及癌热化疗前后的图像传输给存储模块进行存储。存储模块将存储的图像信息传输给比较模块进行比较，比较模块对不同时间电的图像进行比较，当比较出不同时间点的图像及癌热化疗前后的差异时，传输给显示模块，将差异显示给用户，方便用户查看。当比较出不同时间或化疗前后的图像有不同点时，说明化疗有效或病灶有所转移，此时，及时显示出不同图像且通过提示模块提示用户，从而达到及时通知用户化疗有效或病灶有所转移的效果，避免人为的忽略造成严重后果。
优选的，显示模块可选用三维图像显示装置，可使用户查看起来更加方便，直观。
综上所述，当将纳米炭混悬液注射到癌细胞病症周围后，通过增加对应的软件应用及利用癌热化疗仪中的红外发射模块发射红外线，纳米炭吸收红外线升温当其和周围人体组织形成温差时通过探测模块行红外辐射探测，并将其转换为电信号传输给数据采集模块，数据采集模块将采集的数据传输给数据采集模块，数据采集模块对数据进行相应处理，得到相应显示图像。得到淋巴结数量、分布及走向等信息后，利用大功率红外发射模块对病灶周围进行加温，纳米炭比人体其他正常组织更能红外线转化为热量，也就是说，加温后，进入引流淋巴结后的纳米炭的温度能够比身体其他正常组织升温快，利用这个性质可以对病灶淋巴结进行热化疗，热化疗的同时利用温度检测模对病灶淋巴结及人体其他正常组织进行实时温度检测，保证在杀死癌细胞的同时不破坏人体其他正常组织。同时，红外发射模块及大功率红外发射模块分别与时间控制模块连接，实现红外发射模块及大功率红外发射模块的自动控制，且时间控制单元使得红外发射模块及大功率红外发射模块能够精准的控制发射时间，避免人为操作的误差。并且，存储模块对不同时间及化疗前后的显示图像进行对应时间的存储，并通过比较模块进行比较，当比较出不同时间或化疗前后的图像有不同点时，说明化疗有效或病灶有所转移，此时，及时显示出不同图像且通过提示模块提示用户，从而达到及时通知用户化疗有效或病灶有所转移的效果，避免人为的忽略造成严重后果。

Claims (26)

  1. 纳米炭混悬注射剂在制备配合近红外光使用的癌症诊断试剂中的应用。
  2. 纳米炭混悬注射剂在制备配合近红外光使用的热疗试剂的药物中的应用。
  3. 根据权利要求2所述的应用，其特征在于：所述热疗试剂还含有抗癌药。
  4. 根据权利要求3所述的应用，其特征在于：所述抗癌药为阿霉素，表阿霉素，顺铂，紫杉醇或5-氟尿嘧啶。
  5. 根据权利要求3或4所述的应用，其特征在于：热疗试剂含有抗癌药时，纳米炭与抗癌药的重量配比如下；
    抗癌药0.03125-32份，纳米炭0.5-400份；
    优选配比范围：抗癌药0.125-8份，纳米炭1-100份；
    最优配比：抗癌药1份，纳米炭5份；
    或
    采用浓度(μg/ml)比表示：抗癌药∶纳米炭＝0.03125-32∶0.5-400；
    优选配比范围：抗癌药∶纳米炭＝0.125-8∶1-100；
    最优配比：抗癌药∶纳米炭＝1∶5。
  6. 根据权利要求1-5任一项所述的应用，其特征在于：所述近红外光的波长为780-2600nm；优选，所述近红外光的波长为785-1400nm。
  7. 根据权利要求1-5任一项所述的应用，其特征在于：所述纳米炭混悬注射剂含有纳米炭，PVP，生理盐水、pH调节剂，其中纳米炭的粒径为50-250nm；优选粒径范围为100-150nm。
  8. 、根据权利要求1-5任一项所述的应用，其特征在于：所述纳米炭混悬注射剂由纳米炭，PVP，生理盐水、pH调节剂组成，其中纳米炭的粒径为50-250nm；优选粒径范围为100-150nm。
  9. 根据权利要求1-5任一项所述的应用，其特征在于：每1000ml钠米炭混悬注射剂中，含纳米炭2.5-200g、聚乙烯比咯烷酮(PVP)2-200g、pH值调节剂调pH值至6.5-8.0，余量为生理盐水；
    优选，每1000ml纳米炭混悬注射剂中，含纳米炭50g、聚乙烯比咯烷酮(PVP)20g、pH值调节剂调pH值至7.0，余量为生理盐水。
  10. 根据权利要求9所述的应用，其特征在于：所述纳米炭是由黑炭经过有机溶剂除去脂溶性杂质，干燥除去有机物残留；酸洗、碱洗除去无机杂质；水洗除去酸、碱和无机物残留干燥获得。
  11. 根据权利要求9所述的应用，其特征在于：所述pH调节剂可以是任何可以调节pH的化学物质，包括枸橼酸钠、枸橼酸、氢氧化钠、盐酸、醋酸、酒石酸、乳酸；最适宜的pH调节剂是枸橼酸钠。
  12. 根据权利要求9所述的应用，其特征在于：所述纳米炭混悬注射剂的制备方法为：称取聚乙烯吡咯烷酮(优选PVP K30)50g，溶解于300ml生理盐水中；再称取纳米炭20g， 搅拌下加入聚乙烯吡咯烷酮溶液中，再继续加入生理盐水至1000ml；加入振动磨中；室温下振动分散5分钟；用1mol/L枸橼酸钠调节pH至6.5-8.0。
  13. 根据权利要求9所述的应用，其特机在于：所述纳米炭混悬注射剂的制备方法为：称取聚乙烯吡咯烷酮K30 50g，溶解于300ml生理盐水中；再称取纳米炭20g，搅拌下加入聚乙烯吡咯烷酮溶液中，再继续加入生理盐水至1000ml：加入球磨中；室温下球磨分散96小时；用1mol/L枸橼酸钠调节pH至6.5-8.0。
  14. 抗癌药物组合物，其特征在于：含有纳米炭与抗癌药，纳米炭与抗癌药的重量配比如下：
    它含有下述重量配比的组分；抗癌药0.03125-32份，纳米炭0.5-400份；
    优选配比范围：抗癌药0.125-8份，纳米炭1-100份；
    最优配比：抗癌药1份，纳米炭5份；
    或
    采用浓度(μg/ml)比表示：抗癌药∶纳米炭＝0.03125-32∶0.5-400；
    优选配比范围：抗癌药∶纳米炭＝0.125-8∶1-100；
    最优配比：抗癌药∶纳米炭＝1∶5。
  15. 纳米炭淋巴成像仪，包括探测模块，其特征在于，还包括红外发射模块、时间控制模块、数据采集模块、处理模块、存储模块、比较模块及显示模块，所述时间控制模块、数据采集模块、存储模块及显示模块分别与处理模块连接，所述探测模块与数据采集模块连接，红外发射模块与时间控制模块连接，比较模块分别与存储模块及显示模块连接。
  16. 根据权利要求15所述的纳米炭淋巴成像仪，其特征在于，所述红外发射模块为红外发光二极管阵列。
  17. 根据权利要求15所述的纳米炭淋巴成像仪，其特征在于，所述纳米炭淋巴成像仪还包括提示模块，所述提示模块与比较模块连接。
  18. 根据权利要求17所述的纳米炭淋巴成像仪，其特征在于，所述提示模块为LED灯。
  19. 根据权利要求15所述的纳米炭淋巴成像仪，其特征在于，所述探测模块为红外接收器。
  20. 根据权利要求15所述的纳米炭淋巴成像仪，其特征在于，所述显示模块为三维图像显示装置。
  21. 纳米炭淋巴成像仪，包括探测模块，其特征在于，还包括红外发射模块、时间控制模块、数据采集模块、处理模块、存储模块、比较模块及显示模块，所述时间控制模块、数据采集模块、存储模块及显示模块分别与处理模块连接，所述探测模块与数据采集模块连接，红外发射模块与时间控制模块连接，比较模块分别与存储模块及显示模块连接。
  22. 根据权利要求21所述的纳米炭淋巴成像仪，其特征在于，所述红外发射模块为红外发光二极管阵列。
  23. 根据权利要求21所述的纳米炭淋巴成像仪，其特征在于，所述纳米炭淋巴成像仪还包括提示模块，所述提示模块与比较模块连接。
  24. 根据权利要求23所述的纳米炭淋巴成像仪，其特征在于，所述提示模块为LED灯。
  25. 根据权利要求21所述的纳米炭淋巴成像仪，其特征在于，所述探测模块为红外接收器。
  26. 根据权利要求21所述的纳米炭淋巴成像仪，其特征在于，所述显示模块为三维图像显示装置。
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CN203987988U (zh) * 2014-04-11 2014-12-10 重庆莱美药业股份有限公司 纳米炭淋巴成像仪

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CN113548656A (zh) * 2020-06-16 2021-10-26 哈尔滨成程生命与物质研究所 一种具有抗癌生物活性的碳点及制备方法
WO2023284582A1 (zh) * 2021-07-13 2023-01-19 四川瀛瑞医药科技有限公司 一种用于低温热疗的药物制剂及其制备方法和用途

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