KR20240010706A - Bioluminescent capsules for improving blood sugar levels - Google Patents

Abstract

A bioluminescent capsule that emits light within the digestive system and improves metabolic diseases is disclosed. A bioluminescent capsule for improving blood sugar according to an embodiment of the present invention includes a luminescent material that emits light depending on the environment in the digestive tract, a body that accommodates the luminescent material, and a body through which light emitted from the luminescent material is transmitted. It may include a housing and a semi-permeable portion formed on one side of the housing, ventilated with the environment within the digestive tract, and allowing substances within the digestive tract to semi-transparently enter the housing.

Description

Bioluminescent capsules for improving blood sugar levels}

The present invention relates to a bioluminescent capsule that emits light within the digestive system and improves metabolic diseases. More specifically, it relates to a bioluminescent capsule for improving blood sugar that adjusts the activation time of the luminescent material in the capsule so that light is irradiated to the digestive organs related to metabolic diseases, and activates/deactivates luminescence using the environment within the digestive tract.

Metabolic syndrome, which involves diabetes, high blood pressure, lipid metabolism abnormalities, and insulin resistance, has emerged as a major group of diseases that threaten human health due to its high prevalence, and is a threat to national competitiveness in developed countries such as the United States and Europe. It is considered a serious health problem, and enormous human and material capabilities are being invested in solving it. Diseases belonging to the metabolic syndrome are a group of common diseases that increase the risk of occurrence of each other and are related to multifactorial metabolic changes such as aging, stress, and decreased immune function.

In other words, the prevalence of metabolic syndromes such as type 2 diabetes, non-alcoholic fatty liver disease, and obesity has recently been increasing worldwide. As abnormal mucosal thickening occurred in patients with type 2 diabetes and non-alcoholic fatty liver disease, it was confirmed that the secretion of metabolic disease-related hormones (GIP, GLP, etc.) increased in the patient's duodenal mucosa, and the duodenum was mentioned as a key location for non-pharmacological treatment. It is becoming.

In a similar context, due to the side effects of drug treatment for type 2 diabetes and non-alcoholic fatty liver disease and the increase in medical costs through combined treatment, duodenal mucosal resurfacing has recently been studied in many countries around the world. The therapeutic effect of this mucosal resurfacing procedure is confirmed by the replacement of abnormal cells with normal cells, which occurs through ablation of abnormal cells in the duodenal mucosa using high-frequency hydrothermal treatment.

In the case of duodenal surgery using radiofrequency, only one treatment is possible, and the failure rate of the treatment is reported to be around 20%. Although the blood sugar-boosting effect is maintained for about 6-12 months, continuous oral hypoglycemic medication is required, and some patients suffer from hypoglycemia and intestinal perforation after the procedure. , bleeding, etc. have been observed, so there is an urgent need for a non-drug treatment method for metabolic syndrome through effective and safe treatment of the duodenal mucosa. In addition, from the perspective of advanced device treatment, if continuous treatment is required, there is a high possibility that it will cause extreme fatigue to the patient.

Public Patent Publication No. 10-2016-0134951

Therefore, in the present invention, a luminescent protein that is activated under special chemical environmental conditions (O ₂ , glucose, HCO ₃ ) from the duodenum to the jejunum is mounted in a capsule that can be taken by the patient, thereby creating a capsule-type capsule that can irradiate light at the desired target location. It is used as a treatment device for metabolic diseases using a light therapy device.

Accordingly, the problem to be solved by the present invention is to control the activation time of the luminescent material in the capsule so that light is irradiated to the digestive organs related to metabolic diseases, and to develop bioluminescence for improving blood sugar by activating/deactivating luminescence using the environment within the digestive tract. We would like to provide capsules.

Other objects and advantages of the present invention will become clearer from the following detailed description, claims, and drawings.

In order to achieve the problem to be solved, a bioluminescent capsule that emits light in the digestive tract and improves metabolic diseases according to an embodiment of the present invention includes a luminescent material that emits light according to the environment in the digestive tract, and the luminescent material. A housing that accommodates the ash, forms a main body, and transmits light emitted from the luminescent material, is formed on one side of the housing, and is ventilated with the environment in the digestive tract to make the material in the digestive tract semi-transparent. It may include a semi-transparent part that is introduced into the inside.

One end is connected to the semi-permeable portion and further includes a scaffold located inside the housing.

The scaffold transfers the material introduced through the semi-transparent portion to the light-emitting material inside the housing.

The luminescent material is activated by the substance delivered by the scaffold.

It further includes a coating layer coated on the housing and/or the semi-permeable portion, retarding the activity of the luminescent material, and having durability against stomach acid.

The coating layer is methyl acrylate-methacrylic acid copolymer, cellulose acetate succinate, hydroxy propyl methyl cellulose phthalate, hydroxy propyl methyl cellulose acetate succinate (hypromellose acetate succinate), polyvinyl acetate phthalate (PVAP), It is formed of any one selected from the group consisting of methyl methacrylate-methacrylic acid copolymer, sodium alginate, and stearic acid.

The coating layer is formed so that the coating layer is removed from the duodenum or jejunum of the digestive organs.

In the duodenum or jejunum, the housing and the semipermeable portion are exposed to the environment of the duodenum or jejunum.

The luminescent material includes a first luminescent protein that emits light of a first wavelength.

The luminescent material further includes a second luminescent protein that emits light of a second wavelength.

The housing includes a partition separating the first light-emitting protein and the second light-emitting protein.

The luminescent material further includes a luminescent enzyme, and the luminescent material includes Photobacteria luciferase, Firefly luciferase, Railroad worm luciferase, and Renilla luciferase. luciferase), Gaussia luciferase, Metridia luciferase, Cypridiana luciferase, akaluc and Oplophorus luciferase It may be any one selected from the group consisting of.

It further includes a pH sensor to sense pH within the digestive tract, and the pH sensor is located outside the housing.

It further includes an optical sensor for sensing whether or not light is emitted by the luminescent material, and the optical sensor is located within the housing.

It further includes a biological biofuel cell that supplies electricity to the pH sensor or the optical sensor, wherein the biological biofuel cell is located within the housing.

It further includes a magnet so that the capsule can stay in the digestive tract for a certain period of time by a magnetic field applied from the outside, and the magnet is located within the housing (at the end or in the middle).

According to the present invention, a luminescent protein that is activated under special chemical environmental conditions (O ₂ , glucose, HCO ₃ ) from the duodenum to the jejunum is mounted in a capsule that can be taken by the patient to irradiate light at the desired target location. It can be used as a treatment device for metabolic diseases by using a capsule-type light therapy device.

In addition, a bioluminescent capsule for improving blood sugar is provided that adjusts the activation time of the luminescent material in the capsule so that light is irradiated to the digestive organs related to metabolic diseases, and activates/deactivates luminescence using the environment within the digestive tract.

The effects of the present invention are not limited to the effects mentioned above, and other effects of the invention can be clearly understood from the description of the claims.

Figure 1 shows a cross section of a bioluminescent capsule for improving blood sugar according to an embodiment of the present invention.
Figure 2 shows a cross section taken along line II' of Figure 1.
Figure 3 shows a cross-section to explain a partition included in a bioluminescent capsule for improving blood sugar according to an embodiment of the present invention.
Figure 4 shows a cross-section to explain the pH sensor included in the bioluminescent capsule for improving blood sugar according to an embodiment of the present invention.
Figure 5 shows a cross-section to explain the optical sensor included in the bioluminescent capsule for improving blood sugar according to an embodiment of the present invention.
Figure 6 exemplarily shows a treatment method using a bioluminescent capsule for improving blood sugar according to an embodiment of the present invention.
Figure 7 shows experimental results showing the effect of light irradiation by a bioluminescent capsule for improving blood sugar according to an embodiment of the present invention.
Figure 8 shows the results of a human stomach-duodenum simulation experiment to confirm the optimal coating layer conditions of the bioluminescent capsule of the present invention.
Figure 9 is an experimental result showing the removal of the coating layer included in the bioluminescent capsule for improving blood sugar according to an embodiment of the present invention.

The advantages and features of the present invention and methods for achieving them will become clear by referring to the embodiments described in detail below along with the accompanying drawings. However, the present invention is not limited to the embodiments disclosed below and will be implemented in various different forms. The present embodiments only serve to ensure that the disclosure of the present invention is complete and that common knowledge in the technical field to which the present invention pertains is not limited. It is provided to fully inform those who have the scope of the invention, and the present invention is only defined by the scope of the claims. Specific details for implementing the present invention will be described in detail with reference to the drawings attached below. Regardless of the drawings, the same reference numerals refer to the same elements, and “and/or” includes each and all combinations of one or more of the mentioned items.

The terminology used herein is for describing embodiments and is not intended to limit the invention. As used herein, singular forms also include plural forms, unless specifically stated otherwise in the context. As used in the specification, “comprises” and/or “comprising” does not exclude the presence or addition of one or more other elements in addition to the mentioned elements.

Unless otherwise defined, all terms (including technical and scientific terms) used in this specification may be used with meanings that can be commonly understood by those skilled in the art to which the present invention pertains. Additionally, terms defined in commonly used dictionaries are not interpreted ideally or excessively unless clearly specifically defined.

Hereinafter, a bioluminescent capsule for improving blood sugar according to an embodiment of the present invention will be described.

Figure 1 shows a cross-section of a bioluminescent capsule for improving blood sugar according to an embodiment of the present invention, Figure 2 shows a cross-section taken along line II' of Figure 1, and Figure 3 shows an embodiment of the present invention. Figure 4 shows a cross-section for explaining the partition wall included in the bioluminescent capsule for improving blood sugar according to an embodiment of the present invention, and Figure 4 shows a cross-section for explaining the pH sensor included in the bioluminescent capsule for improving blood sugar according to an embodiment of the present invention. , Figure 5 shows a cross-section to explain the optical sensor included in the bioluminescent capsule for improving blood sugar according to an embodiment of the present invention.

With reference to FIGS. 1 to 5, a bioluminescent capsule 10 that emits light within the digestive tract and improves metabolic diseases according to an embodiment of the present invention will be described.

The bioluminescent capsule 10 for improving blood sugar according to an embodiment of the present invention includes a luminescent material 210 that emits light depending on the environment within the digestive tract, accommodates the luminescent material 210, forms a main body, and emits light. A housing 110 through which the light emitted from the material 210 is transmitted, is formed on one side of the housing 110, and is ventilated with the environment within the digestive tract to semi-transparently transmit substances within the digestive tract. It may include a semi-transparent portion 120 introduced into 110).

The bioluminescent capsule 10 for improving blood sugar level of the present invention is an oral type that can be ingested through the mouth and can be formed into a tablet form. In the present invention, metabolic disease has substantially the same meaning as metabolic syndrome, and metabolic disease may mean, for example, diabetes, obesity, hyperlipidemia, hypertension, non-alcoholic fatty liver disease, etc.

First, the bioluminescent capsule 10 for improving blood sugar may include a housing 110 forming the main body. The housing 110 accommodates the luminescent material 210, which will be described later. Additionally, when the luminescent material 210 emits light under specific conditions, the housing 110 can transmit the emitted light toward the digestive system. For this purpose, the housing 110 is preferably made of a transparent polymer material. Additionally, the material forming the housing 110 is preferably made of a material that is harmless to the human body.

Materials forming the housing 110 include silicone, polystyrene, polymethyl methacrylate, polyethyl methacrylate, polybutyl methacrylate, ethyl cellulose, polyvinyl pyridine, polyacrylonitrile, and melamine-formaldehyde polymer. It may be any one transparent resin selected from the group consisting of.

The housing 110 can protect the luminescent material 210 within the capsule 10 from being exposed to the environment within the digestive tract while the capsule 10 floats in the digestive tract. The housing 110 may be formed in a hollow shape with an empty center to accommodate the light emitting material 210, and the hollow may be filled with the light emitting material 210.

Next, a semi-transparent portion 120 may be formed and positioned on one side of the housing 110.

The semi-permeable portion 120 is ventilated with the environment within the digestive tract, allowing substances within the digestive tract to enter the housing 110 semi-permeably. Here, the digestive organ may be the duodenum or jejunum.

That is, the semi-permeable portion 120 can semi-transparently introduce oxygen (O ₂ ), glucose, HCO ₃ , etc. distributed in the duodenum or jejunum into the housing 110 . On the other hand, the luminous material 210 present in the housing 110 may not leak out of the housing 110.

The semi-transparent portion 120 may be formed on only one side, or may be formed on both sides of the housing 110, such as one side and the other side. The number of semi-transparent portions 120 formed may be adjusted depending on the design performance of the capsule 10.

Meanwhile, the semi-permeable portion 120 is made of cellulose-based (Cellulose acetate, Cellulose triacetate), polyamide, polyimide, polyethersulfone, and polyamideimide-polyethyleneimine. It can be formed as one of the following: The diameter of the semi-transparent portion 120 may be 500 μm to 1 mm, the thickness may be 100 to 200 μm, and pores of 1 to 10 nm are formed in the semi-transparent portion 120.

Next, one end is connected to the semi-permeable portion 120, and the scaffold 310 is located inside the housing 110. The scaffold 310 transfers substances in the digestive tract introduced from the semi-permeable portion 120 into the housing 110.

More specifically, when the capsule 10 passes through the oral cavity, esophagus, and stomach due to the peristalsis of the digestive system and reaches the duodenum or jejunum, substances in the duodenum or jejunum enter the housing 110 through the semi-permeable portion 120. It can be. Such substances may include oxygen (O ₂ ), glucose, HCO ₃ , etc., as described above. The substances introduced through the semi-permeable portion 120 may be diffused and transferred to an area within the housing 110 through the scaffold 310 connected to the semi-permeable portion 120. As a result, the materials can be delivered to the light emitting material 210 contained in the housing 110 by the scaffold 310.

Meanwhile, the light-emitting material 210 may be activated by the materials delivered by the scaffold 310. This will be described later.

The scaffold 310 may be formed of a material similar to the semi-permeable portion 120. That is, the scaffold 310 is made of cellulose (Cellulose acetate, Cellulose triacetate), polyamide, polyimide, polyethersulfone, and polyamideimide-polyethyleneimine. It can be formed as one of the following: The diameter of the scaffold 310 may be 500 ㎛ to 1 mm, and may be formed in a tube shape to extend in the longitudinal direction of the capsule 10. At this time, the tube thickness of the scaffold 310 may be 100 to 200 μm. Meanwhile, the length of the scaffold 310 may be similar to the longitudinal direction of the capsule 10. Pores of 1 to 10 nm are formed in the scaffold 310. Materials introduced through the pores may diffuse into the internal space of the housing 110.

If the semi-transparent portion is formed on both sides, such as one side and the other side, one end of the scaffold 310 may be connected to one side of the semi-transparent portion, and the other side of the scaffold 310 may be connected to the other side of the semi-transparent portion. In this case, the scaffold 310 may be positioned to penetrate the interior of the housing 110.

Next, the bioluminescent capsule 10 for metabolic disease according to an embodiment of the present invention may include a luminescent material 210 that emits light depending on the environment within the digestive tract.

The luminescent material 210 is accommodated in the housing 110, and when the substances in the digestive tract described above are introduced into the housing 110 and the substances are delivered to the inside of the housing 110 by the scaffold 310, the The light emitting material 210 may be activated by substances.

More specifically, when the capsule 10 passes through the oral cavity, esophagus, and stomach due to the peristalsis of the digestive system and reaches the duodenum or jejunum, substances in the duodenum or jejunum enter the housing 110 through the semi-permeable portion 120. It can be. Such substances may include oxygen (O ₂ ), glucose, HCO ₃ , etc., as described above. The substances introduced through the semi-permeable portion 120 may be diffused and transferred to an area within the housing 110 through the scaffold 310 connected to the semi-permeable portion 120. As a result, the materials can be delivered to the light emitting material 210 contained in the housing 110 by the scaffold 310. Accordingly, the light-emitting material 210 may be activated by the introduced materials and light emission may be generated.

The luminescent material 210 may include a luminescent enzyme and ATP (adenosine triphosphate) that activate the light emission of the luminescent protein. That is, the luminescent material 210 may be made of a mixture of luminescent protein, luminescent enzyme, and ATP. Light emission occurs when a luminescent protein reacts with ATP, etc. and is oxidized, and when a luminescent protein is oxidized, a luminescent enzyme can promote the oxidation reaction.

The luminescent protein is of the luciferin or akalumine series, and materials extracted from nature or newly synthesized through recombination using adenovirus vectors, nanoparticles, and quantum lights (maximizing luminescence intensity and time) can be used. Most bioluminescence may have a limited light irradiation time, emitting light for only a few seconds. Therefore, the density of the luminescent protein can be maximized and introduced into the luminescent capsule 10, and the luminescent enzyme can be introduced into the luminescent capsule 10 to maintain a low concentration compared to the luminescent protein. In addition, by forming a semi-permeable membrane layer within the light-emitting capsule 10, the space within the light-emitting capsule 10 can be divided into an area into which the light-emitting protein enters and an area into which the light-emitting enzyme enters. At this time, the light-emitting protein and luminescent enzyme located in the area divided by the semi-permeable membrane layer can slowly combine due to the osmotic pressure difference between the two substances and the semi-permeable membrane layer. For this purpose, the concentration of luminescent protein and luminescent enzyme can be configured as 2:1, 3:1, 4:1, etc. Through this, the light emission time can be extended. The relatively low light intensity of these luminescent proteins uses the metronome principle to maximize the effective amount of light delivered to small intestine cells by lengthening the emission time. In order to increase the time of light irradiation delivered to small intestine cells, the number of optical capsules taken can be increased, or the magnetic field of an extracorporeal magnet can be used to minimize movement of magnet-equipped optical capsules within the small intestine. Meanwhile, when the light-emitting material 210 is activated to emit light having a first wavelength, the light-emitting material may include a first light-emitting protein 211. At this time, the first wavelength may be, for example, 630 nm or 850 nm. Additionally, the first wavelength may be a wavelength in the visible light region or a wavelength in the near-infrared region.

When the light-emitting material 210 includes only the first light-emitting protein 211 as the light-emitting protein, the light-emitting material 210 can emit light with a single wavelength.

If the light-emitting material 210 emits light having a second wavelength, the light-emitting material 210 may include a second light-emitting protein 212. Here, the second wavelength may be, for example, 630 nm or 850 nm. If the above-mentioned first wavelength is 630 nm, the second wavelength is 850 nm, and if the first wavelength is 850 nm, the second wavelength is 630 nm.

In the present invention, the appropriate wavelength was used to determine the blood sugar control effect of light therapy using an LED-based light therapy catheter, and the conditions applied to the device were compared and analyzed to derive wavelength, energy, and time settings that could maximize the treatment effect. .

The light-emitting material 210 may emit composite light. For example, the light-emitting material 210 may emit light having the above-described first wavelength and light having the second wavelength. To this end, the light-emitting material 210 may be made of a mixture of a first light-emitting protein 211 that emits light with a first wavelength and a second light-emitting protein 212 that emits light with a second wavelength.

When the light-emitting material 210 is made of a complex light-emitting protein, such as including a first light-emitting protein 211 and a second light-emitting protein 212, the efficiency of the light-emitting protein is improved and the resolution of the light emitted is increased. For this purpose, a partition wall (410 in FIG. 3) may be formed within the housing 110.

That is, in order to separately accommodate the first light-emitting protein 211 and the second light-emitting protein 212 within the housing 110, the housing 110 is configured to contain the first light-emitting protein 211 and the second light-emitting protein within the housing 110. It may include a partition 410 that separates the protein 212. The first light-emitting protein 211 and the second light-emitting protein 212 are each accommodated in separate spaces within the housing 110 by the partition 410. At this time, if the first light-emitting protein 211 is a luciferin series, the second light-emitting protein 212 may be an akalumine series. On the other hand, if the first light-emitting protein 211 is an akalumine series, the second light-emitting protein 212 may be a luciferin series.

In addition, the first or second light emitting protein contained in the light emitting material 210 may be a light emitting protein combined with Adeno-associated virus Adenovirus vector, E. coli, nanoparticles, and photon lighting, including GFP and RFP. Fluorescent or luminescent proteins such as these may also be included.

Meanwhile, the light-emitting enzyme (not shown) included in the light-emitting material 210 is Photobacteria luciferase, Firefly luciferase, Railroad worm luciferase, and Renilla luciferase. Renilla luciferase, Gaussia luciferase, Metridia luciferase, Cypridiana luciferase, akaluc and Oplophorus luciferase It may be any one selected from the group consisting of (Oplophorus luciferase).

Meanwhile, the first or second light-emitting protein in the other space separated by the partition is Photobacteria luciferase, Firefly luciferase, Railroad worm luciferase, and Renilla luciferase, Gaussia luciferase, Metridia luciferase, Cypridiana luciferase, Oplophorus luciferase Luminescent activation may be achieved through reaction with at least one of the luminescent enzymes.

To activate the luminescent material 210, it is desirable to shake the capsule at a constant speed when taking the capsule. As a result, the first luminescent protein and the second luminescent protein can come into contact with each other and emit light due to the crack in the partition, thereby preparing the activation of the luminescent material 210 and making it more smooth in the area of the digestive tract where the luminescent material 210 is activated. Light can be emitted clearly. You can take the capsule by shaking it several times before taking it so that the luminescent protein binds to the enzyme and becomes part of the bioluminescence reaction.

The method of filling the housing 110 with the luminescent material 210 may be as follows.

For example, if the housing 110 is divided into two parts and formed by combining them, the housing on one side is filled with a luminous material, and then the housing on the other side is combined with the housing on one side to form the housing 110. The luminescent material 210 can be filled during the completion process.

Next, after the housing 110 is completed, the housing 110 can be filled with a luminescent material using a syringe needle. That is, when a needle is inserted into the completed housing 110, the needle penetrates the housing 110, and the end of the needle is inserted into the housing 110. The luminescent material 210 is filled into the housing 110 through the end of the inserted injection needle, and the luminescent material 210 is accommodated inside the housing 110.

The air-pocket that is created during the filling process of these luminescence-related proteins and enzymes minimizes the movement of the capsule in the duodenum and small intestine through the buoyancy effect in the semi-solid and liquid form of food in the duodenum area, thereby infiltrating small intestine cells. The desired treatment effect is expected by providing an appropriate optical signal from the luminescent function capsule.

Meanwhile, for optimal therapeutic effect through light signals, 2-3 luminescent capsules of the present invention can be taken at a time, and light signal transmission in the small intestine can be optimized by taking them three times a day. These air pockets are necessary in the process of combining luminescent proteins and enzymes, and as the air pockets disappear from the large intestine due to the exhaustion of oxygen through the luminescent process, the buoyancy effect is lost and is discharged out of the body along with general digested substances.

Meanwhile, when taking the capsule 10, it is preferable to shake the capsule at a constant speed to activate the luminescent material 210. As a result, the activity of the luminescent material 210 is prepared, and light emission can occur more smoothly in the area of the digestive system where the luminescent material 210 is activated.

If light is emitted by the luminescent material in the digestive tract, phototherapy can be performed by luminescence by the capsule 10 of the present invention in the digestive tract. More specifically, the digestive organ here may be the duodenum or jejunum. The activity of the luminescent material 210 is suppressed while the capsule 10 passes through the esophagus and stomach by a coating layer to be described later.

When the capsule 10 reaches the duodenum or jejunum, the coating layer 101 covering the housing 110 and the semi-permeable portion 120 is removed. When the coating layer 101 is removed and the semi-permeable portion 120 is exposed in the duodenum or jejunum, substances distributed in the duodenum or jejunum can be introduced into the housing 110. Here, the substances may be, for example, oxygen (O ₂ ), glucose, HCO ₃ , etc.

When these substances are introduced into the housing 110 and diffused into the housing 110 by the scaffold 310, the substances are transferred to the light emitting material 210 in the housing 110. As a result, the luminescent material 210 is activated to emit light, and the light can be irradiated to the tissue area of the duodenum or jejunum through the housing 110, which is a transparent material capable of transmitting light.

Meanwhile, the housing 110 is formed of a light-transmitting material, but in order to increase the efficiency with which the light emitted within the capsule 10 is irradiated to the duodenum or jejunum through the housing 110, a light diffusion or A light-transmitting material can be additionally coated. The additionally coated light diffusing or light transmitting material may be substantially the same as the material forming the housing 110 described above.

By irradiated light, metabolic syndrome that may originate from the tissue area of the duodenum or jejunum can be treated by light irradiation. In other words, metabolic syndrome such as diabetes, obesity, hyperlipidemia, high blood pressure, non-alcoholic fatty liver disease, etc. can be improved by light emission from the bioluminescent capsule 10 for improving blood sugar level of the present invention.

Next, the bioluminescent capsule 10 for metabolic disease according to an embodiment of the present invention is coated on the housing 110 and the semi-permeable portion 120, and delays the activity of the luminescent material 210, It may include a coating layer 101 that is durable against stomach acid.

The coating layer 101 prevents the housing 110 and the semi-permeable portion 120 of the capsule 10 from being exposed within the digestive tract for a certain period of time. That is, after ingestion of the capsule 10, the housing 110 and the semi-permeable portion 120 can be prevented from being exposed within the digestive tract for approximately 4 hours.

This is to promote the luminescent activity of the capsule 10 in the duodenum or jejunum, which are digestive organs related to metabolic diseases. That is, the coating layer 101 may be formed on the housing 110 to be removed from the duodenum or jejunum of the digestive organs.

This is because approximately 4 hours after ingestion of the capsule 10, the capsule 10 can reach the duodenum or jejunum, and the coating layer 101 is gradually removed by gastric acid or the like while reaching the capsule 10. For this purpose, the coating layer 101 is preferably formed of a material that is durable against stomach acid, etc. This coating layer may cover the entire housing or may be configured to coat only the semi-transparent portion 120.

As the coating layer 101 is removed near the duodenum or jejunum, the housing 110 and the semi-permeable portion 120 may be exposed to the environment of the duodenum or jejunum. As a result, substances distributed within the duodenum or jejunum are introduced into the housing 110 through the exposed semi-permeable portion 120. Therefore, when taking it orally, the photocapsule is shaken several times to begin the combination of the bioluminescent substance with the photoenzyme, but the most important element, oxygen, and other substances necessary for bioluminescence flow into the photocapsule from the duodenum, allowing the photocapsule to start emitting light effectively from the duodenum. do.

A detailed explanation for this has been described above, so repeated explanations will be omitted.

Meanwhile, the coating layer 101 is preferably formed of a material that is durable against the pH of stomach acid. The coating layer 101 is methyl acrylate-methacrylic acid copolymer, cellulose acetate succinate, hydroxy propyl methyl cellulose phthalate, hydroxy propyl methyl cellulose acetate succinate (hypromellose acetate succinate), and polyvinyl acetate phthalate (PVAP). ), methyl methacrylate-methacrylic acid copolymer, sodium alginate, and stearic acid.

The thickness of the coating layer 101 may be 10-300㎛, preferably 100-170㎛. As a result, it is possible to prevent the housing 110 and the semi-permeable portion 120 from being exposed to gastric acid in parts of the digestive system where exposure is not desired (eg, stomach, esophagus, etc.).

Next, in order to sense pH within the digestive tract, the capsule 10 may further include a pH sensor 510. At this time, the pH sensor 510 may be located outside the housing 110. The pH sensor 510 can sense the pH of the digestive tract where the capsule is located by sensing the pH of substances introduced through the semi-permeable portion 120.

The pH sensor 510 can sense the pH within the digestive tract and transmit this information to an external terminal (eg, cell phone, PC, tablet PC, etc.). For example, pH information measured in the stomach and pH information measured in the duodenum are transmitted. Since the pH of the stomach and the duodenum are different, when the difference in pH level is sensed, an external observer can recognize that the capsule 10 has moved from the stomach to the duodenum.

Meanwhile, an optical sensor 520 may be further included to sense whether or not the light emitting material 210 of the capsule 10 emits light within the digestive tract. At this time, the optical sensor 520 may be located within the housing 110. By sensing the degree of light emission from the capsule 10 using the optical sensor 520, it is possible to measure whether sufficient light for phototherapy is irradiated to the digestive system.

For the operation of the pH sensor 510 and the optical sensor 520, electrical energy is required. In order to supply electrical energy to the pH sensor 510 and the optical sensor 520, the capsule 10 may include a biological bio fuel cell 530. The biological bio fuel cell 530 may be located within the housing 110. For example, the biological bio fuel cell 530 can generate electrical energy by oxidizing glucose. The biological bio fuel cell 530 may be electrically connected to each of the pH sensor 510 and the optical sensor 520.

Meanwhile, the capsule 10 may not include the biological bio fuel cell 530. At this time, the pH sensor 51 can receive power in the following manner. In other words, it is possible to detect the pH of the area where the optical capsule passes through a wire-less power, wearable, external radiofrequency pH sensor monitor.

Referring to FIG. 4, the capsule 10 according to an embodiment of the present invention is equipped with a magnet (magnet) so that the capsule 10 can be fixed to the digestive organ (e.g., duodenum or jejunum) requiring treatment for a certain period of time. 610) may be included. The magnet 610 may be located within the housing 110.

When a magnetic field is applied to the magnet 610 from the outside (see FIG. 6), the capsule 10 containing the magnet 610 is fixed to a specific location within the digestive tract for a certain period of time by the electromagnetic force between the external magnetic field and the magnet 610. It can be stopped. At this time, when the light emission of the capsule 10 is activated, the area of the digestive tract where the capsule 10 is fixed may be irradiated with light by the light emission of the capsule 10.

For example, when trying to irradiate light to the duodenum, a doctor or observer obtains pH information using the above-described pH sensor 510, and if it is determined through this that the location of the capsule 10 is near the duodenum, an external magnet device ( A magnetic field is applied to the capsule 10 through 1000, and the capsule 10 can be fixed to the duodenum for a certain period of time by the electromagnetic force between the magnet 610 and the external magnetic field. At this time, when the light emission of the capsule 10 is activated, the capsule 10 is fixed to the duodenum for a certain period of time, thereby maximizing the effect of light irradiation of the capsule 10 on the duodenum.

According to an embodiment of the present invention, the bioluminescent capsule 10 for improving blood sugar has its activation suppressed for a certain period of time (approximately 4 hours) after ingestion, and is used in digestive organs (e.g., duodenum, jejunum) that require light treatment to improve metabolic diseases. Activation may proceed in . That is, the activity of the luminescent material 210 in the capsule 10 is delayed by the coating layer 101, and after a certain period of time during which the coating layer 101 is removed, the luminescent material 210 is activated by substances in the duodenum that have moved. When activated, light can be irradiated to digestive organs that require phototherapy. As a result, metabolic diseases such as diabetes, obesity, hyperlipidemia, high blood pressure, and non-alcoholic fatty liver disease can be improved.

Meanwhile, depending on the course of treatment, multiple capsules can be taken to maximize light irradiation in the duodenum or jejunum. In particular, whether to take additional capsules 10 may be determined based on the amount of light irradiation measured through an optical sensor included in the capsule 10.

In other words, the amount of light required for treating metabolic diseases can be adjusted by adjusting the number and/or number of administrations of the capsules 10. In other words, you can take 2 or 3 capsules at a time, or you can adjust the dosage of capsules 3 times a day.

When the capsule 10 passes through the duodenum or jejunum and reaches the large intestine, the substance that can activate the luminescent material becomes scarce, so light emission may not occur. That is, the luminescent material of the capsule can be deactivated. The capsule 10 that has passed the large intestine cannot be digested and may be discharged out of the body through feces.

Hereinafter, the present invention will be described in more detail through examples. These examples are only for illustrating the present invention in more detail, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .

<Example 1: Manufacturing of a luminescent capsule containing a luminescent material>

A capsule container made of silicone was prepared. The container is used as a housing, and the external size of the housing is substantially similar to the final size of the capsule being manufactured. The silicone housing was 28 mm long and 13 mm in diameter.

Inside the housing, a commercial thin-film pH sensor, magnet, and biofuel cell to provide power to the pH sensor were mounted. These devices were purchased commercially.

A semi-permeable membrane was formed on one side and the other side of the housing. The semi-permeable membrane was made of cellulose with a diameter of 800 μm and a thickness of 150 μm. Additionally, a scaffold was formed to be connected to the semi-permeable membrane and positioned within the housing. The scaffold was made of cellulose and was formed into a tube shape with a diameter of 800㎛.

Using an LED-based light therapy catheter, the blood sugar control effect of light therapy was confirmed, and the conditions applied to the device were compared and analyzed to derive wavelength, energy, and time settings that could maximize the treatment effect.

The housing was filled with a luminous material. Among the luminescent materials, 1g of acarumin series material was used as the luminescent protein, 1g of akaluc was used as the luminescent enzyme, and 1g of ATP was also used. The luminescent material was filled into the housing using an injection needle. Then, the surface of the housing was coated with hydroxypropyl methyl cellulose phthalate, and a luminescent capsule filled with the luminescent material was finally manufactured. At this time, the final length of the capsule was 28 mm and the diameter was 13 mm.

<Experimental Example 1: Blood sugar control effect of luminescent capsule>

After administering the prepared capsules to volunteers three times at a time, we examined the effect on the volunteers' blood sugar control. After taking the drug, a magnetic field was applied to the volunteer's duodenum, taking into account the pH information transmitted from the capsule and the time elapsed (4 hours) after taking the drug. After applying the magnetic field for about 1 hour, changes in the volunteer's blood sugar were measured. Before taking the drug, the volunteer's blood sugar level was measured in advance as a control.

Referring to Figure 7, the blood sugar control effect according to light irradiation could be seen. Referring to FIG. 7, in the control group, almost no change in blood sugar over time was detected, but when light with a wavelength of 630 nm was irradiated, it was found that blood sugar decreased for 60 minutes from the beginning. Additionally, when light with a wavelength of 850 nm was irradiated, it was found that the blood sugar reduction effect lasted up to 180 minutes.

In particular, when a composite light (dual wavelength) of 630 nm wavelength and 850 nm wavelength is irradiated, the effect of light of 630 nm wavelength is effective from the beginning to 60 minutes, and the effect of light of 850 nm wavelength is effective from 60 minutes to 180 minutes. It occurred in combination. In other words, it was found that in the case of combined light, the blood sugar reduction effect was maintained for each light.

Accordingly, the bioluminescent capsule 10 for improving blood sugar according to the present invention has a blood sugar reducing effect and will contribute to improving the condition of patients with metabolic syndrome.

<Example 2: Preparation of luminescent capsule>

Two light-emitting capsules of different lengths were manufactured using the same materials and methods as the light-emitting capsules of Example 1. The lengths of the manufactured luminescent capsules were 20 mm and 18 mm, respectively, and each diameter was 13 mm. That is, the housing surface of each light-emitting capsule was coated with hydroxypropyl methyl cellulose phthalate.

<Experimental Example 2: Whether the coating layer is removed from the light-emitting capsule>

Using a human-mimicking gastric-duodenal simulator, the time for food to remain in the stomach was predicted to estimate the time the coating layer should be maintained in the luminescent capsule and the actual luminescence time. It was confirmed that the residual amount (number of color markers in the stomach, Figure 8a) and the amount of discharge (Figure 8b) converged 160 minutes after the food was flushed, and 4 hours was set as the standard indicator of the residual time in the stomach.

In addition, after the light-emitting capsule prepared in Example 2 was introduced into the gastrointestinal simulator, it was measured whether the coating layer coated on the housing of the light-emitting capsule was removed in the gastrointestinal simulator.

The results are shown in Figure 9. Referring to Figure 9, it was found that after 4 hours (240 minutes), about 60% of the coating layer of the luminescent capsule according to an embodiment of the present invention in a camouflaged state was removed (approximately 40% of the coating layer remained). That is, when the luminescent capsule of the present invention was ingested orally, it was found that a significant portion of the coating layer was removed during the 4 hours it passed through the stomach.

Accordingly, when the light-emitting capsule passes through the stomach and near the duodenum or jejunum, the housing or semi-permeable portion from which the coating layer has been removed may be exposed to the outside. Due to this exposure, the light-emitting capsule can emit light in the duodenum or jejunum, and the light emitted through the exposed housing can be irradiated to the vicinity of the duodenum or jejunum.

Although the embodiments of the present invention have been described above, the present invention is not limited to the above embodiments and can be manufactured in various different forms, and those skilled in the art will understand the technical idea of the present invention. It will be understood that it can be implemented in other specific forms without changing the essential features. Therefore, the embodiments described above should be understood in all respects as illustrative and not restrictive.

10: Capsule 101: Coating layer 110: Housing
120: semi-transparent portion 210: luminescent material 310: scaffold
410: partition wall 510: pH sensor 520: optical sensor
530: Living bio fuel cell 610: Magnet

Claims (11)

In the bioluminescent capsule that emits light within the digestive tract and improves blood sugar,
A luminescent material that emits light depending on the environment within the digestive tract;
a housing that accommodates the light-emitting material and transmits light emitted from the light-emitting material;
a semi-permeable portion provided in the housing, through which substances in the digestive tract are semi-permeable; and
Includes a scaffold accommodated in the housing, connected to the semi-transparent portion, and transmitting the material semi-permeable through the semi-transparent portion to the luminescent material, wherein the luminescent material is transmitted by the material delivered through the scaffold. A bioluminescent capsule for improving blood sugar, characterized by being activated. According to claim 1,
A bioluminescent capsule for improving blood sugar, further comprising a coating layer coated on at least one of the housing and the semi-permeable portion, retarding the activity of the luminescent material, and having durability against stomach acid. According to clause 2,
The coating layer is methyl acrylate-methacrylic acid copolymer, cellulose acetate succinate, hydroxy propyl methyl cellulose phthalate, hydroxy propyl methyl cellulose acetate succinate (hypromellose acetate succinate), polyvinyl acetate phthalate (PVAP), A bioluminescent capsule for improving blood sugar, characterized in that it is formed of any one selected from the group consisting of methyl methacrylate-methacrylic acid copolymer, sodium alginate, and stearic acid. According to clause 3,
A bioluminescent capsule for improving blood sugar, characterized in that the coating layer is removed from the duodenum or jejunum of the digestive organs. According to claim 1,
The luminescent material is,
A first light-emitting protein that emits light of a first wavelength; and
A bioluminescent capsule for improving blood sugar, characterized in that it further comprises a second luminescent protein that emits light of a second wavelength. According to clause 5,
The bioluminescent capsule for improving blood sugar, characterized in that the housing further includes a partition separating the first light-emitting protein and the second light-emitting protein. According to claim 1,
The luminescent material further includes a luminescent enzyme,
The luminescent material includes Photobacteria luciferase, Firefly luciferase, Railroad worm luciferase, Renilla luciferase, and Gaussia luciferase. luciferase), Metridia luciferase, Cypridiana luciferase, akaluc, and Oplophorus luciferase. Bioluminescent capsules for improving blood sugar levels. According to claim 1,
A bioluminescent capsule for improving blood sugar, further comprising a pH sensor provided outside the housing to sense pH within the digestive tract. According to clause 8,
A bioluminescent capsule for improving blood sugar, further comprising an optical sensor provided inside the housing to sense whether light is emitted by the luminescent material. According to clause 9,
A bioluminescent capsule for improving blood sugar, characterized in that it further includes a living biofuel cell provided inside the housing and supplying electricity to the pH sensor or the optical sensor. According to claim 1,
A bioluminescent capsule for improving blood sugar, further comprising a magnet provided inside the housing to allow the capsule to remain in the digestive tract for a certain period of time by a magnetic field applied from the outside.