CN114425082A - Device for tracking malignant tumor target of gastrointestinal tract - Google Patents
Device for tracking malignant tumor target of gastrointestinal tract Download PDFInfo
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- CN114425082A CN114425082A CN202111672575.4A CN202111672575A CN114425082A CN 114425082 A CN114425082 A CN 114425082A CN 202111672575 A CN202111672575 A CN 202111672575A CN 114425082 A CN114425082 A CN 114425082A
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Abstract
The invention belongs to the technical field of medical treatment, and particularly relates to a device for tracking malignant tumor targets of gastrointestinal tracts, which is of a capsule structure, wherein the capsule structure comprises a capsule shell and contents, and the capsule shell is made of gelatin, purified water, dilute acid, a plasticizer and chitosan; the structure of the contents is as follows: the drug loading device comprises a mother nucleus, wherein a plurality of branch buds are dispersedly arranged around the periphery of the mother nucleus and are distributed in a radial or star shape, and a drug loading ball is arranged at the end part of each branch bud, which is far away from the mother nucleus; the mother nucleus and the branch buds are both made of gelatin, purified water and a plasticizer; the drug-loaded ball is made of gelatin, purified water, a plasticizer and an anti-tumor drug; and the capsule shell or the medicine carrying ball is provided with a tracking mark for identifying the position of the malignant tumor. The device of the invention can track the target of gastrointestinal tract tumor.
Description
Technical Field
The invention belongs to the technical field of medical treatment, and particularly relates to a device for tracking a malignant tumor target of a gastrointestinal tract.
Background
Malignant tumor is cancer, which is usually characterized by abnormal cell differentiation and proliferation, unregulated growth, invasive and metastatic biological characteristics, and the pathogenesis of malignant tumor is usually multifactorial and multistep, and is related to various factors such as smoking, occupational exposure, environmental pollution, heredity and the like. The clinical manifestations of malignant tumor may be lump, pain, ulcer, bleeding, etc., with local symptoms, systemic symptoms, and even tumor metastasis.
The malignant tumor examination includes gene detection, imaging examination, tumor marker detection, pathological tissue examination and other measures, and the diagnosis result is given after comprehensive judgment of various examination results.
The treatment of malignant tumor includes various treatment means such as surgery (resection, etc.), chemotherapy (killing tumor cells by chemical drugs), radiotherapy (killing tumor cells by radiation), targeted therapy (targeted combination and killing tumor cells by tumor-specific drugs), and the like.
Gastrointestinal tumors mainly occur in the stomach, small intestine or large intestine, and can be diagnosed or assisted to treat diseases through a gastroscope or an endoscope, and whether the malignant tumors are diagnosed or treated, the accurate or more accurate target tracking of the tumor positions can improve the diagnosis efficiency and the treatment efficiency and reduce the damage to normal cells. Especially for malignant tumor, the target tracking of its position is very helpful for understanding its position of diffuse metastasis and treating the focus of diffuse metastasis.
The prior art lacks a target tracking device aiming at gastrointestinal tract tumors.
Disclosure of Invention
In order to solve the technical problem, the invention provides a device for tracking a malignant tumor target of a gastrointestinal tract.
The invention aims to provide a device for tracking a malignant tumor target of a gastrointestinal tract, which is of a capsule structure, wherein the capsule structure comprises a capsule shell and contents, and the capsule shell is prepared from the following raw material components in parts by weight: 50-70 parts of gelatin, 50-77 parts of purified water, 0.5-1 part of dilute acid (0.1-0.5mol/L hydrochloric acid), 0.5-1 part of plasticizer (glycerol) and 1-3 parts of chitosan; wherein the weight ratio of the gelatin to the purified water is 1: 1-1.1;
the structure of the contents is as follows: the drug loading device comprises a mother nucleus, wherein a plurality of branch buds are dispersedly arranged around the periphery of the mother nucleus and are distributed in a radial or star shape, and a drug loading ball is arranged at the end part of each branch bud, which is far away from the mother nucleus;
the mother nucleus and the branch buds are prepared by mixing gelatin, purified water and a plasticizer according to the weight part ratio of 100:80-90: 1-2;
the medicine carrying ball is prepared from the following raw materials in parts by weight: 33-55 parts of gelatin, 30-50 parts of purified water, 0.8-1.2 parts of plasticizer and 30-40 parts of anti-tumor drug; in the raw materials for preparing the drug-loaded ball, the weight part ratio of gelatin to purified water is 1.1:1, and the weight part of the anti-tumor drug is less than or equal to that of the gelatin;
the capsule shell or the medicine carrying ball is provided with a tracking mark for identifying the position of the malignant tumor.
Preferably, the above device for tracking a target of a malignant tumor in the gastrointestinal tract, the method for preparing the drug-loaded pellet is as follows:
weighing gelatin, purified water, plasticizer and antitumor drugs according to the weight part ratio;
continuously stirring gelatin, purified water and a plasticizer under the conditions that the vacuum degree is-0.10 to-0.05 MPa and the temperature is 80 to 90 ℃ to obtain a gelatin solution, and cooling to 50 to 60 ℃ after the gelatin solution has no bubbles;
adding the anti-tumor drug, fully mixing, placing in a drug-loaded ball mold, and drying and molding; or preparing the anti-tumor drug into a solution as a raw material of a content and a gelatin solution as a raw material of a capsule shell, preparing the anti-tumor drug into a capsule by using a capsule machine, and drying and forming the capsule to obtain the drug-loaded ball.
Preferably, the device for tracking the target of the gastrointestinal malignant tumor comprises a spherical or ellipsoidal mold, and the drying condition is that the mold is dried at 20-40 ℃ and the moisture content of the drug-loaded ball is less than 5%.
Preferably, the above device for tracking a target of a malignant tumor in the gastrointestinal tract, the content is prepared by the following steps:
preparing a content mold with the structural shape of the content, and placing a medicine carrying ball at the position of the medicine carrying ball in the content mold;
mixing gelatin, purified water and plasticizer (glycerol) according to the weight part ratio of 100:80-90:1-2, continuously stirring at 80-90 ℃ under the condition that the vacuum degree is-0.10-0.05 MPa, cooling to 50-60 ℃ when the solution is bubble-free, adding the solution into a content mold, wrapping the medicine-carrying ball by the solution, and drying at 20-40 ℃ until the water content is lower than 5% to obtain the content.
Preferably, the above device for tracking a gastrointestinal malignant tumor target is prepared by the following steps:
preparing a capsule shell mold having a capsule shape, which may be an ellipsoid shape or a spherical shape or a hemispherical shape or a semi-ellipsoid shape, and placing the contents in the capsule shell mold;
weighing the raw materials according to the weight part ratio of the capsule shell, and uniformly mixing chitosan and dilute acid to obtain a chitosan material for later use;
mixing gelatin, purified water and a plasticizer, continuously stirring at the vacuum degree of-0.10 to-0.05 MPa and the temperature of 80 to 90 ℃, cooling to 50 to 60 ℃ when the solution has no bubbles, adding a chitosan material, and continuously stirring to fully mix the materials to obtain a capsule shell solution;
the capsule shell solution or the medicine carrying ball is provided with a tracking mark for identifying the position of the malignant tumor;
and adding the capsule shell solution into a capsule shell mold, wrapping the content with the solution, and drying at 20-40 ℃ until the water content is lower than 5% to obtain the device for tracking the target of the gastrointestinal malignant tumor.
Preferably, according to the device for tracking the malignant tumor target of the gastrointestinal tract, the outer surface of the content is firstly sprayed with a layer of edible liquid preservative film to infiltrate the outer surface of the content, and then the content is placed into the capsule shell mold.
Preferably, in the device for tracking the target of the gastrointestinal malignant tumor, 3 to 5 parts of a drug efficacy enhancer of an anti-tumor drug is further added into the drug-loaded ball.
Preferably, the above device for tracking the target of the gastrointestinal malignant tumor has a mass ratio of the capsule shell to the content of 1: 1-1.5.
Preferably, the device for tracking the target of the malignant tumor of the gastrointestinal tract further comprises a guide wire and a catheter, the catheter is used for being inserted into the gastrointestinal cannula, a plurality of perforations are dispersedly arranged on the outer wall of the catheter, one capsule structure is arranged at each perforation, the diameter of each perforation is smaller than that of the drug-loaded ball, the guide wire is inserted into the catheter, the head end pipe of the guide wire penetrates out of the perforation and penetrates into the capsule structure, and the tail end of the guide wire extends out of the catheter.
Preferably, the above-mentioned device for tracking a target of a malignant tumor in the gastrointestinal tract is provided with an image marker that can be identified by an image, such as an X-ray opaque or an ultrasound opaque material.
Compared with the prior art, the invention has the following beneficial effects:
1. the chitosan adopted by the invention is dissolved in dilute acid to be in a sticky state, the beta-1, 4-glycosidic bond of the chitosan in the dilute acid can be slowly hydrolyzed to generate the chitosan with low relative molecular mass, and the chitosan is dissolved in an acid solution to form a positive charged cationic group, has strong adsorbability, can be used as a drug sustained-release material, and has good affinity for human cells. After the capsule is taken by human body, the capsule shell is gradually decomposed in gastric juice, the chitosan in the capsule shell is released, the chitosan is compatible with cells in stomach and intestine, and the stimulation of capsule components to human body cells is reduced.
2. One function of the drug-loaded ball is to load anti-tumor drugs, which are convenient for targeted therapy, the anti-tumor drugs can be targeted probe drugs for inhibiting the growth of malignant tumors, the targeted probe drugs have detectable tracking marks such as fluorescent marks, and the positions of the malignant tumor cells are identified and tracked by detecting the positions of the drugs. The anti-tumor drug can also be a chemotherapeutic drug without a probe, and nanoparticles and the like which can be tracked and identified are required to be prepared, for example, a hydrophobic drug nanocapsule which is prepared by the patent CN 104721843B and can be traced by near infrared fluorescence and has pH response is dried to constant weight at 20-40 ℃, then is crushed into powder with the particle size of less than 200 meshes, is fully mixed with the chemotherapeutic drug, and is then used for preparing a drug-loaded ball.
The medicine carrying ball has the other function of being filled inside the capsule shell, after the capsule is used by a human body, the medicine carrying ball can be close to cells due to the affinity and the adsorption capacity of chitosan to the cells, the capsule shell is gradually decomposed in gastrointestinal fluid, the medicine carrying ball is released, the anti-tumor medicine on the medicine carrying ball is directly close to the cells, the medicine is not contacted with non-tumor parts such as an oral cavity, the non-therapeutic effect between the gastrointestinal fluid, saliva and the like and the anti-tumor medicine is reduced, and the medicine utilization rate is improved. If the medicine carrying ball is provided with the tracking marks for identifying the malignant tumor positions, the discomfort caused by the contact of the tracking marks with other parts of the human body can be prevented.
3. The content is arranged in a radial shape or a star shape, each drug carrying ball is separated, different anti-tumor drugs can be loaded on different drug carrying balls, the time for releasing the drugs is different along with the different gelatin content on different drug carrying balls, different anti-tumor drugs can be released in different time and act on tumor cells, the release of different drugs at different time can be completed through one-time administration, and the trouble that a patient frequently records the drug taking time is avoided. In addition, because the radial or star-shaped shape has a plurality of branch buds and the medicine carrying balls, and the weight ratio of gelatin and purified water in the branch buds, the mother core and the medicine carrying balls in the contents is larger than the weight ratio of corresponding gelatin and purified water in the capsule shell, the degradation speed of the contents in the gastrointestinal tract is slow, and after the capsule shell is decomposed, the branch buds and the medicine carrying balls of the residual contents can be quickly attached to tumor tissues to better exert the antitumor effect, so that the structure of the contents is particularly suitable for a directional administration route.
4. The drug effect enhancer provided by the invention can enhance the inhibition rate of the antitumor drug on tumor cells.
Drawings
FIG. 1 is a schematic diagram of the apparatus for tracking a target of a malignant tumor in the gastrointestinal tract according to embodiments 1 to 8;
FIG. 2 is a schematic diagram I of the apparatus for gastrointestinal malignant tumor target tracking according to example 9;
fig. 3 is a schematic structural diagram of the device for tracking a target of a malignant tumor in the gastrointestinal tract according to embodiment 9.
Detailed Description
In order that those skilled in the art will better understand the technical solutions of the present invention, the present invention will be further described with reference to the following specific embodiments and the accompanying drawings.
In the description of the present invention, reagents used are commercially available and methods used are conventional in the art, unless otherwise specified.
In the description of the present invention, it is to be understood that the terms "central," "longitudinal," "lateral," "length," "width," "thickness," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," "outer," "clockwise," "counterclockwise," "axial," "radial," "circumferential," and the like are used in the orientations and positional relationships indicated in the drawings for convenience in describing the invention and to simplify the description, and are not intended to indicate or imply that the referenced device or element must have a particular orientation, be constructed and operated in a particular orientation, and are not to be considered limiting of the invention.
The terms "first", "second" and "first" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature; in the description of the present invention, "a plurality" means two or more unless otherwise specified.
In the description of the present invention, unless otherwise expressly specified or limited, the terms "mounted," "connected," "secured," and the like are to be construed broadly, e.g., as meaning either a fixed connection, a removable connection, or an integral part; can be mechanically or electrically connected; they may be directly connected or indirectly connected through intervening media, or they may be connected internally or in any other suitable relationship, unless expressly stated otherwise. The specific meanings of the above terms in the present invention can be understood by those skilled in the art according to specific situations.
In the description of the present invention, unless otherwise explicitly specified or limited, a first feature "on" or "under" a second feature may be directly contacting the first feature or the second feature through intervening media. Also, a first feature "on," "over," and "above" a second feature may be directly or diagonally above the second feature, or may simply indicate that the first feature is at a higher level than the second feature. A first feature being "under," "below," and "beneath" a second feature may be directly under or obliquely under the first feature, or may simply mean that the first feature is at a lesser elevation than the second feature.
Example 1
A device for target tracking of gastrointestinal malignant tumors is shown in figure 1, and is a capsule structure, wherein the capsule structure comprises a capsule shell 1 and contents, and the capsule shell 1 is prepared from the following raw material components in parts by weight: 70 parts of gelatin, 77 parts of purified water, 1 part of 0.2mol/L hydrochloric acid, 1 part of glycerol and 3 parts of chitosan; wherein the weight part ratio of the gelatin to the purified water is 1: 1.1;
the structure of the contents is as follows: the compound biological agent is characterized by comprising a mother nucleus 2, wherein a plurality of branch buds 3 are dispersedly arranged around the periphery of the mother nucleus 2, the branch buds 3 are radially distributed, and a medicine carrying ball 4 is arranged at the end part of each branch bud 3, which is far away from the mother nucleus 2;
the mother nucleus 2 and the branch bud 3 are prepared by mixing gelatin, purified water and glycerol according to the weight part ratio of 100:80: 1;
the medicine carrying ball 4 is prepared from the following raw materials in parts by weight: 55 parts of gelatin, 50 parts of purified water, 0.8 part of glycerol and 40 parts of anti-tumor medicine; in the raw materials for preparing the medicine carrying ball 4, the weight ratio of gelatin to purified water is 1.1: 1;
the capsule shell 1 or the medicine carrying ball 4 is provided with a tracking mark for identifying the position of the malignant tumor.
Example 2
A device for gastrointestinal malignant tumor target tracking is of a capsule structure, the capsule structure comprises a capsule shell 1 and contents, and the capsule shell 1 is prepared from the following raw material components in parts by weight: 50 parts of gelatin, 50 parts of purified water, 0.5 part of 0.5mol/L hydrochloric acid, 0.5 part of glycerol and 1 part of chitosan; wherein the weight ratio of the gelatin to the purified water is 1: 1;
the structure of the contents is as follows: the compound biological agent is characterized by comprising a mother nucleus 2, wherein a plurality of branch buds 3 are dispersedly arranged around the periphery of the mother nucleus 2, the branch buds 3 are radially distributed, and a medicine carrying ball 4 is arranged at the end part of each branch bud 3, which is far away from the mother nucleus 2;
the mother nucleus 2 and the branch bud 3 are prepared by mixing gelatin, purified glycerol and water according to the weight part ratio of 100:80: 2;
the medicine carrying ball 4 is prepared from the following raw materials in parts by weight: 44 parts of gelatin, 40 parts of purified water, 1.2 parts of glycerol and 35 parts of anti-tumor medicine; in the raw materials for preparing the medicine carrying ball 4, the weight ratio of gelatin to purified water is 1.1: 1;
the capsule shell 1 or the medicine carrying ball 4 is provided with a tracking mark for identifying the position of the malignant tumor.
Example 3
A device for gastrointestinal malignant tumor target tracking is of a capsule structure, the capsule structure comprises a capsule shell 1 and contents, and the capsule shell 1 is prepared from the following raw material components in parts by weight: 60 parts of gelatin, 66 parts of purified water, 0.8 part of 0.1mol/L hydrochloric acid, 0.8 part of glycerol and 2 parts of chitosan; wherein the weight part ratio of the gelatin to the purified water is 1: 1.1;
the structure of the contents is as follows: the compound fertilizer comprises a mother nucleus 2, a plurality of branch buds 3 are dispersedly arranged around the periphery of the mother nucleus 2, the branch buds 3 are distributed in a star shape, and a medicine carrying ball 4 is arranged at the end part of each branch bud 3, which is far away from the mother nucleus 2;
the mother nucleus 2 and the branch bud 3 are prepared by mixing gelatin, purified water and glycerol according to the weight part ratio of 100:90: 2;
the medicine carrying ball 4 is prepared from the following raw materials in parts by weight: 33 parts of gelatin, 30 parts of purified water, 1.1 parts of glycerol and 30 parts of anti-tumor medicine; in the raw materials for preparing the medicine carrying ball 4, the weight ratio of gelatin to purified water is 1.1: 1;
the capsule shell 1 or the medicine carrying ball 4 is provided with a tracking mark for identifying the position of the malignant tumor.
Example 4
A method for manufacturing the device for tracking a malignant tumor target in the gastrointestinal tract according to embodiment 1 comprises the following steps:
step one, preparing a medicine carrying ball 4
Weighing gelatin, purified water, glycerol and an anti-tumor drug according to the weight part ratio of the raw materials of the drug-loaded ball 4 in the embodiment 1;
continuously stirring gelatin, purified water and glycerol at 90 deg.C under vacuum degree of-0.05 MPa to obtain gelatin solution, and cooling to 60 deg.C when there is no bubble in the gelatin solution;
adding the anti-tumor drug, fully mixing, placing in a drug-loaded ball mold, and drying and molding to obtain a drug-loaded ball 4;
the medicine carrying ball mould is round, the drying condition is 20 ℃ or 40 ℃, and the water content of the medicine carrying ball 4 is lower than 5%;
step two, preparing the content
Preparing a content mold with a content structure shape, and placing the medicine carrying ball 4 at the position of the medicine carrying ball 4 in the content mold;
mixing the gelatin, the purified water and the glycerol according to the weight part ratio of the raw materials of the mother nucleus and the branch bud in the embodiment 1, continuously stirring under the conditions that the vacuum degree is minus 0.10MPa and the temperature is 80 ℃, cooling to 50 ℃ after the solution has no bubbles, adding the solution into a content mold, enabling the solution to wrap the drug-carrying ball 4, drying at 20 ℃ and enabling the water content to be lower than 5% to obtain a content;
step three, preparing the capsule structure
Preparing a capsule shell mold having the structure of the capsule shell 1, which can be an ellipsoid shape or a spherical shape or a hemispherical shape or a semi-ellipsoid shape, and placing the contents in the capsule shell mold;
weighing the raw materials according to the weight part ratio of the raw materials of the capsule shell 1 in the embodiment 1, and uniformly mixing chitosan and dilute acid to obtain a chitosan material for later use;
mixing gelatin, purified water and glycerol, continuously stirring at 80 deg.C under vacuum degree of-0.10 MPa, cooling to 50 deg.C when the solution has no bubble, adding chitosan material, and continuously stirring to fully mix the materials to obtain capsule shell solution;
the capsule shell solution or the medicine carrying ball 4 is provided with a tracking mark for identifying the position of the malignant tumor;
and adding the capsule shell solution into a capsule shell mold, wrapping the content with the solution, and drying at 20 ℃ until the water content is lower than 5% to obtain the device for tracking the gastrointestinal malignant tumor target.
Example 5
A method for manufacturing the device for tracking a malignant tumor target in the gastrointestinal tract according to embodiment 2 comprises the following steps:
step one, preparing a medicine carrying ball 4
Weighing gelatin, purified water, glycerol and an anti-tumor drug according to the weight part ratio of the raw materials of the drug-loaded ball 4 in the embodiment 2;
continuously stirring gelatin, purified water and glycerol at 80 deg.C under vacuum degree of-0.10 MPa to obtain gelatin solution, and cooling to 50 deg.C when there is no bubble in the gelatin solution;
adding the anti-tumor drug, fully mixing, placing in a drug-loaded ball mold, and drying and molding to obtain a drug-loaded ball 4;
the medicine carrying ball mold is in an ellipsoidal shape, the drying condition is drying at 30 ℃, and the water content of the medicine carrying ball 4 is lower than 5%;
step two, preparing the content
Preparing a content mold with a content structure shape, and placing the medicine carrying ball 4 at the position of the medicine carrying ball 4 in the content mold;
mixing the gelatin, the purified water and the glycerol according to the weight part ratio of the raw materials of the mother nucleus and the branch bud in the embodiment 2, continuously stirring under the conditions that the vacuum degree is minus 0.05MPa and the temperature is 90 ℃, cooling to 60 ℃ after the solution has no bubbles, adding the solution into a content mold, enabling the solution to wrap the drug-carrying ball 4, drying at 40 ℃ and enabling the water content to be lower than 5% to obtain a content;
step three, preparing the capsule structure
Preparing a capsule shell mold having the structure of the capsule shell 1, which can be an ellipsoid shape or a spherical shape or a hemispherical shape or a semi-ellipsoid shape, and placing the contents in the capsule shell mold;
weighing the raw materials according to the weight part ratio of the raw materials of the capsule shell 1 in the embodiment 2, and uniformly mixing chitosan and dilute acid to obtain a chitosan material for later use;
mixing gelatin, purified water and glycerol, continuously stirring at 90 deg.C under vacuum degree of-0.05 MPa, cooling to 60 deg.C when the solution has no bubble, adding chitosan material, and continuously stirring to fully mix the materials to obtain capsule shell solution;
the capsule shell solution or the medicine carrying ball 4 is provided with a tracking mark for identifying the position of the malignant tumor;
and adding the capsule shell solution into a capsule shell mold, wrapping the content with the solution, and drying at 40 ℃ until the water content is lower than 5% to obtain the device for tracking the gastrointestinal malignant tumor target.
Example 6
A method for manufacturing the device for tracking a malignant tumor target in the gastrointestinal tract according to example 3, which is substantially the same as the method described in example 4, except that: the weight part formulation of each part was the formulation of example 3.
Example 7
A method for manufacturing the device for tracking a malignant tumor target in the gastrointestinal tract according to example 1 is substantially the same as the method described in example 4, except that:
the medicine carrying ball 4 is prepared from the following raw materials in parts by weight: 55 parts of gelatin, 50 parts of purified water, 0.8 part of glycerol, 40 parts of anti-tumor medicine and 3 parts of efficacy enhancer.
The preparation method of the medicine carrying ball 4 comprises the following steps:
weighing gelatin, purified water, glycerol and an anti-tumor drug according to the weight part ratio of the raw materials of the drug-loaded ball 4 in the example 7;
continuously stirring gelatin, purified water and glycerol at 90 deg.C under vacuum degree of-0.05 MPa to obtain gelatin solution, and cooling to 60 deg.C when there is no bubble in the gelatin solution;
adding the anti-tumor drug and the drug effect enhancer, fully mixing, placing in a drug-loaded ball mold, and drying and molding to obtain a drug-loaded ball 4;
the medicine carrying ball mold is circular, the drying condition is 20 ℃ or 40 ℃, and the water content of the medicine carrying ball 4 is lower than 5%.
Example 8
A method for manufacturing the device for tracking a malignant tumor target in the gastrointestinal tract according to example 1 is substantially the same as the method described in example 7, except that:
the medicine carrying ball 4 is prepared from the following raw materials in parts by weight: 55 parts of gelatin, 50 parts of purified water, 0.8 part of glycerol, 40 parts of anti-tumor medicine and 5 parts of efficacy enhancer.
It should be noted that the capsule structure prepared by the method described in the above examples 4-8 can be directly orally taken, and the specific dosage is calculated according to the effective content of the anti-tumor drug in the capsule structure and the required amount of the anti-tumor drug in the patient.
It should be noted that, in the method described in the above embodiments 4 to 8, the outer surface of the content is first sprayed with an edible liquid preservative film to soak the outer surface of the content, and then placed in a capsule shell mold, such as the liquid preservative film described in CN104073000A, which has an antibacterial effect to prevent the antitumor drug from being contaminated by bacteria, and can also form an interface with the capsule shell 1, because both the capsule shell 1 and the preservative film need to be decomposed in vivo, the time for the decomposition of the content to start is significantly later than that of the capsule shell 1, so that the shape of the content can still maintain a good radial or star shape when the content is directly contacted with the internal environment.
Example 9
2-3, a guide wire 5 and a guide tube 6 are added on the basis of any one of the embodiments 1-3, the guide tube 6 is used for being inserted into a gastrointestinal intubation tube 7, the gastrointestinal intubation tube 7 is selected from an enema or an intubation tube 7 for injecting liquid diet into the stomach in the prior art, a plurality of perforations are dispersedly arranged on the outer wall of the guide tube 6, each perforation is provided with one capsule structure, the diameter of each perforation is smaller than that of the medicine carrying ball 4, the guide wire 5 is inserted into the guide tube 6, the head end tube of the guide wire penetrates out of the perforation and penetrates into the capsule structure, and the tail end of the guide wire extends to the outside of the guide tube 6, so that the guide wire is convenient to be operated by hands. The guide wire 5 is used for fixing or releasing the capsule structure.
The working principle of the embodiment is as follows: inserting a guide wire 5 into the catheter 6, making a head end pipe of the guide wire 5 penetrate through the perforation and penetrate into the capsule structure, and extending the tail end of the guide wire to the outside of the catheter 6, then puncturing the head end of the guide wire 5 with a prepared device for tracking the malignant tumor target of the gastrointestinal tract of the capsule structure, paying attention to not puncture the medicine carrying ball 4, preferably, placing the capsule structure against the outer wall of the catheter 6 to obtain a medicine delivery catheter for standby; for a malignant tumor position needing targeted tracking and drug administration, a gastrointestinal cannula 7 (which is a gastric cannula or an intestinal cannula) is inserted into an affected part and is as close to the malignant tumor position as possible, the insertion method of the gastrointestinal cannula 7 refers to the prior art, then the head end of a drug delivery catheter is inserted into the gastrointestinal cannula 7 first, then the drug delivery catheter is controlled from the tail end of the drug delivery catheter, the drug delivery catheter gradually enters the gastrointestinal cannula 7, the end part with a drug-carrying ball 4 is as close to the malignant tumor as possible, see fig. 2, then any one guide wire 5 is pulled out, the drug-carrying ball 4 is separated from the corresponding guide wire 5 under the blocking of a perforation, a drug administration operation is completed, see fig. 3, the drug administration position can be judged by tracking the position of a capsule structure, and along with the pulling out of all the guide wires 5, the drug administration operation of all the drug-carrying balls 4 is completed, and the gastrointestinal cannula 7, the catheter 6 and the guide wire 5 are pulled out.
It should be noted that the outer wall of the catheter 6 is provided with image markers that can be identified by images, such as X-ray or ultrasound-opaque materials, to facilitate observation of the administration procedure.
Preferably, different anti-tumor drugs are placed in different drug carrying balls 4, and the position of the last drug carrying ball is adjusted according to the position of the last drug carrying ball, so that each anti-tumor drug can be ensured to be targeted to treat malignant tumors as far as possible.
Experimental example 1 inhibition of gastric cancer cell Activity
The drug effect enhancers selected in the experimental example are vitamin E and capsaicin, and the cell strains selected in the experiment are three cell strains MGC-803, BGC-823 and SGC-7901 of gastric cancer.
The activity of each cell strain is detected by adopting an MTT colorimetric method, a blank control without adding any medicine is used, and an experimental group with the medicine is used. Firstly, carrying out adherent culture on cell strains, incubating for about 48 hours, then respectively adding corresponding drugs according to the drug concentration settings of a blank control and an experimental group, continuously incubating for 48 hours, washing cells, replacing a new culture medium, then treating MTT and dimethyl sulfoxide, finally measuring the light absorption value of 570nm, and calculating the cell activity.
The calculation result of the gastric cancer cell activity is shown in table 1, the inhibition rate of the blank control is 0, and the result shows that the vitamin E and the capsaicin have good effect of inhibiting the cancer cell activity, and the inhibition rate is up to more than 50%.
TABLE 1 Effect of different doses of drugs on the cellular Activity of tumor cells
Example 2 experiment for enhancing antitumor Effect
The drug effect enhancers selected in the experimental example are vitamin E and capsaicin, the anti-tumor drugs selected are apatinib mesylate tablets (Jiangsu Henry pharmaceutical Co., Ltd.), and the cell strains selected in the experiment are three cell strains of gastric cancer MGC-803, BGC-823 and SGC-7901. In the addition amount of the table 2, the apatinib mesylate tablets are used in terms of apatinib.
The activity of each cell strain is detected by adopting an MTT colorimetric method, a blank control without adding any medicine is used, and an experimental group with the medicine is used. Firstly, carrying out adherent culture on cell strains, incubating for about 48 hours, then respectively adding corresponding drugs according to the drug concentration settings of a blank control and an experimental group, continuously incubating for 48 hours, washing cells, replacing a new culture medium, then treating MTT and dimethyl sulfoxide, finally measuring the light absorption value of 570nm, and calculating the cell activity.
The calculation results of the gastric cancer cell activity are shown in table 2, in table 2 below, the inhibition rate of the blank control is regarded as 0, the drug addition concentration corresponds to the sequence of the drug names, and the results show that the combination of vitamin E and apatinib and the combination of capsaicin and apatinib has the effect of inhibiting cancer cells compared with the effect of pure apatinib.
TABLE 2 Effect of different doses of drugs on the cellular Activity of tumor cells
It should be noted that, the connection relation of the components not specifically mentioned in the present invention is the default of the prior art, and the connection relation of the structures is not described in detail since it does not relate to the invention point and is a common application of the prior art.
It should be noted that, when the present invention relates to a numerical range, it should be understood that two endpoints of each numerical range and any value between the two endpoints can be selected, and since the steps and methods adopted are the same as those in the embodiment, in order to prevent redundancy, the present invention describes a preferred embodiment. While preferred embodiments of the present invention have been described, additional variations and modifications in those embodiments may occur to those skilled in the art once they learn of the basic inventive concepts. Therefore, it is intended that the appended claims be interpreted as including the preferred embodiment and all changes and modifications that fall within the scope of the invention.
It will be apparent to those skilled in the art that various changes and modifications may be made in the present invention without departing from the spirit and scope of the invention. Thus, if such modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include such modifications and variations.
Claims (10)
1. The device for tracking the target of the malignant tumor of the gastrointestinal tract is characterized by being of a capsule structure, wherein the capsule structure comprises a capsule shell (1) and contents, and the capsule shell (1) is prepared from the following raw material components in parts by weight: 50-70 parts of gelatin, 50-77 parts of purified water, 0.5-1 part of dilute acid, 0.5-1 part of plasticizer and 1-3 parts of chitosan; wherein the weight ratio of the gelatin to the purified water is 1: 1-1.1;
the structure of the contents is as follows: the medicine carrying device comprises a mother nucleus (2), a plurality of branch buds (3) are dispersedly arranged around the periphery of the mother nucleus (2), and medicine carrying balls (4) are arranged at the end parts, far away from the mother nucleus (2), of the branch buds (3);
the mother nucleus (2) and the branch buds (3) are prepared by mixing gelatin, purified water and a plasticizer according to the weight part ratio of 100:80-90: 1-2;
the medicine carrying ball (4) is prepared from the following raw materials in parts by weight: 33-55 parts of gelatin, 30-50 parts of purified water, 0.8-1.2 parts of plasticizer and 30-40 parts of anti-tumor drug;
the capsule shell (1) or the medicine carrying ball (4) is provided with a tracking mark for identifying the position of the malignant tumor.
2. The device for gastrointestinal malignant tumor target tracking according to claim 1, wherein the drug-loaded pellet (4) is prepared by the following method:
weighing gelatin, purified water, plasticizer and antitumor drugs according to the weight part ratio;
continuously stirring gelatin, purified water and a plasticizer under the conditions that the vacuum degree is-0.10 to-0.05 MPa and the temperature is 80 to 90 ℃ to obtain a gelatin solution, and cooling to 50 to 60 ℃ after the gelatin solution has no bubbles;
adding the anti-tumor drug, fully mixing, placing in a drug-loaded ball mold, and drying and molding; or preparing the anti-tumor drug into solution as a raw material of the content and gelatin solution as a raw material of the capsule shell, preparing the solution into capsules by using a capsule machine, and drying and forming the capsules to obtain the drug-loaded balls (4).
3. The device for gastrointestinal tract malignant tumor target tracking according to claim 2, wherein the drug-loaded ball mold is spherical or ellipsoidal, the drying condition is 20-40 ℃, and the moisture content of the drug-loaded ball (4) is less than 5%.
4. The device of claim 2, wherein the contents are prepared by the following steps:
preparing a content mold with a content structure shape, and placing the medicine carrying ball (4) at the position of the medicine carrying ball (4) in the content mold;
mixing gelatin, purified water and plasticizer according to the weight ratio of 100:80-90:1-2, continuously stirring at the vacuum degree of-0.10-0.05 MPa and the temperature of 80-90 ℃, cooling to 50-60 ℃ after the solution has no bubbles, adding the solution into a content mold, wrapping the medicine-carrying ball (4) with the solution, and drying at the temperature of 20-40 ℃ until the water content is lower than 5% to obtain the content.
5. The device for gastrointestinal tract malignant tumor target tracking according to claim 4, wherein the device for gastrointestinal tract malignant tumor target tracking is prepared by the following steps:
preparing a capsule shell mold having the shape of a capsule shell (1), and placing the contents in the capsule shell mold;
weighing the raw materials according to the weight part ratio of the capsule shell (1), and uniformly mixing chitosan and dilute acid to obtain a chitosan material for later use;
mixing gelatin, purified water and a plasticizer, continuously stirring at the vacuum degree of-0.10 to-0.05 MPa and the temperature of 80 to 90 ℃, cooling to 50 to 60 ℃ when the solution has no bubbles, adding a chitosan material, and continuously stirring to fully mix the materials to obtain a capsule shell solution;
the capsule shell solution or the medicine carrying ball (4) is provided with a tracking mark for identifying the position of the malignant tumor;
and adding the capsule shell solution into a capsule shell mold, wrapping the content with the solution, and drying at 20-40 ℃ until the water content is lower than 5% to obtain the device for tracking the target of the gastrointestinal malignant tumor.
6. The device of claim 5, wherein the outer surface of the contents is coated with an edible liquid preservative film to infiltrate the outer surface of the contents, and then placed in the capsule shell mold.
7. The device for gastrointestinal malignant tumor target tracking according to claim 1, wherein 3-5 parts of the drug efficacy enhancer of the antitumor drug is further added into the drug-loaded ball (4).
8. The device for gastrointestinal tract malignant tumor target tracking according to claim 1, wherein the mass ratio of the capsule shell (1) to the content is 1: 1-1.5.
9. The device for tracking the malignant tumor target in the gastrointestinal tract according to any one of claims 1 to 8, further comprising a guide wire (5) and a catheter (6), wherein the catheter (6) is used for being inserted into the gastrointestinal cannula (7), the outer wall of the catheter (6) is provided with a plurality of dispersed perforations, each perforation is provided with one capsule structure, the diameter of each perforation is smaller than that of the drug-loaded ball (4), the guide wire (5) is inserted into the catheter (6), the head end tube of the guide wire penetrates through the perforations and penetrates into the capsule structures, and the tail end of the guide wire extends out of the catheter (6).
10. The device for gastrointestinal tract malignant tumor target tracking according to claim 9, wherein the outer wall of the catheter (6) is provided with image markers that can be identified by images.
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CN112717265A (en) * | 2020-12-27 | 2021-04-30 | 河北医科大学第二医院 | Target tracking device and method for gastrointestinal tumor |
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