TW201138788A - A drug carrier for gastrointestinal ulcer - Google Patents

Abstract

A drug carrier for gastrointestinal ulcer comprises: a micro-spheroid including a substrate and particles, wherein the particles are distributed over the substrate, also under the cover of the substrate; and a coat, to cover up the micro-spheroid. In the present invention, the particles are selected from clinical drugs using for gastrointestinal ulcer treatment which are co-enveloped in the substrate consisted of alginate and the coat consisted of chitosan to provide the drug carrier for gastrointestinal ulcer.

Description

201138788 VI. Description of the Invention: TECHNICAL FIELD OF THE INVENTION The present invention relates to a pharmaceutical carrier, and more particularly to a sustained release pharmaceutical carrier for use in the elimination of ulcers. [Prior Art] Gastrointestinal ulcer refers to the destruction of the gastrointestinal mucosa leading to inflammation, hemorrhage and perforation, resulting in a decrease in the defense ability of the mucosa, and hydrogen ions easily infiltrate into the mucosa to cause damage. It is one of the common civilized diseases of modern people; Usually for poor eating habits, excessive emotional reactions, endocrine disorders, stomach acid knife will be strong or caused by Helicobacter pylori (ugly sputum infection, etc.. In the treatment of / Xiaohuadao ulcers to take 1. antacid, 2. anti- Histamine and 3. proton pump inhibitor (pr〇t〇n pump inhibitor 'ρρι) have certain effects; antacids are generally marketed stomach drugs, mostly magnesium-aluminum pharmacy, the main function is acid It protects the mucosa and tissue repair, and has a curative effect on mild gastrointestinal symptoms. However, it is short (4) and has only a short-term inhibitory effect; anti-Qiyi's inhibition of the tissue of the chemotherapeutic cells is reduced by histamine activity. _ Langfa is unacceptable, however, the role of m-woven amine is a systemic influence. 'There is a strong side effect, which may cause physical damage; and m is the most commonly used therapeutic drug for cancer-related diseases. , is a weak test 'usually with enteric film granules _ application, absorbed by the small intestine and then act on the stomach wall' main effect to inhibit the stomach wall of the lining three Wei: put, child into the stomach cavity, inhibit gastric acid production, to treat L! Refer to the digestive ulcer of X. Although ppi has a better effect on the treatment of digestive ulcers, 201138788, 乂2, there are still restrictions; firstly, the preparation of PPI should be given to the activation of parietal cells. The timing of the drug is preferably before eating, and the PPI is slowed down. 11. The effect of the remission can be seen only a few days after taking the drug, affecting the efficacy of the emergency patient, and the administration time of the ppI is limited. 24 hours ^ gastric acid &gt; secretion 'can not maintain the role of nighttime, leading to patients suffering from burning and pain, in addition, the pharmacokinetics of m on the emergence of great angina, may affect other drugs Ingredients; therefore, regarding the PPI in patients with body_transmission and release is an important challenge for the treatment of digestive tract lining. In recent years, due to the rise of drug carriers, the development of related drug formulations has gradually increased to improve the therapeutic effect of PPI. The duration of action in the patient's body is reduced and the side effects may be reduced. For example, as shown in the Republic of China Patent No. 200613011, "Adhesive Nanocomposite Drug Delivery System", it is known that the f-species The drug, the carrier, the chitin polymer is encapsulated in a surface-modified silica dioxide gel to form a nanoporous composite material, and the nanoporous composite material and the drug for treating Helicobacter pylori infection are Effective treatment of peptic ulcer caused by Helicobacter pylori. Chitin is a biocompatible and biodegradable material with mucosal adsorption and the ability to act as a drug release carrier. In the case of encapsulating chitin, the surface is modified. The cerium dioxide is gelled to form an interpenetrating network of cerium oxide and chitin nanoporous composites. The cerium oxide gel is very stable in acid, providing dense in the nanoporous composite. The tangled structure can be significantly delayed in the acidic environment. Therefore, in the stomach environment, the composite can effectively delay the release rate of the drug, so that the drug can be prolonged in the patient's body. Time role. A second pharmaceutical carrier for digestive ulcers, such as US Patent No. 201138788 No. 2007/0281015, "Powder-type acid-resistant pharmaceutical composition and preparation method thereof", which discloses a pharmaceutical composition for oral use and a preparation method thereof , comprising sodium alginate, a proton pump inhibitor and at least one soluble or partially soluble antacid agent for treating hyperacidity; wherein the antacid is usually an inorganic soluble salt or a microsoluble salt, such as sister The salt, such as heavy carbon _ or nitrogen oxide surface, can be too acidic in the stomach towel; _ brown nucleus forms a viscous suspension (colloid) in the stomach environment to protect the activity of the gastric mucosa; The proton pump inhibitor is absorbed into the stomach in the intestine; the second type of Wei can be used to protect the proton pump inhibitor from the inside of the pharmaceutical composition by means of encapsulation, thereby avoiding the destruction of gastric acid. In addition, as disclosed in the Republic of China Patent No. 464514, a pharmaceutical carrier for a third type of peptic ulcer is an oral pharmaceutical dosage form containing a proton pump inhibitor and an antacid or an alginate containing an acid-sensitive proton pump inhibitor. The first component, one or more selected from the group consisting of a antacid, an alginate, and a mixture thereof, and a third component of a pharmaceutically acceptable group as desired. The above-mentioned conventional drug carrier for digestive ulcers mainly uses a polymer material (such as alginate) as a main carrier component to coat a therapeutic agent (such as a proton pump inhibitor) to cause a sustained release effect; However, the single coating configuration composed of the polymer material is easily damaged during the digestion process, especially in the stomach suffering from gastric acid erosion, which affects the sustained release effect, resulting in a limited time for prolonging the action of the medicament; The time of staying in the digestive tract is short-lived and cannot directly exert therapeutic effects on the affected part. However, the first drug carrier for digestive ulcers, which contains a chitin complex, can adsorb the spot film and directly affect the affected part, but The encapsulation of chitin and cerium oxide 201138788 is also unable to withstand gastric acid for a long time and effectively exerts a sustained release effect, failing to improve the therapeutic effect of the agent; further, the drug carrier is not completely produced by: decomposable Made of sexual materials, it may cause adverse effects on the human body and needs further evaluation. SUMMARY OF THE INVENTION The present invention is to improve the above disadvantages, and to provide a pharmaceutical carrier for cancer of the digestive tract, and the main object of the invention is to solve the problem that the drug carrier is easily attacked by gastric acid, so that the sustained release effect cannot be maintained for a long time. A second object of the present invention is to provide a drug carrier for peptic ulcer, which can be used as a gastrointestinal tract and is directly used as a secret part to enhance the therapeutic effect. A further object of the present invention is to provide a pharmaceutical carrier for digestive ulcers which is completely made of a biodegradable material to avoid side effects. In order to achieve the foregoing object, the technical means and the achievable effects of the present invention include: a pharmaceutical carrier for gastrointestinal cancer, comprising: a microsphere comprising a matrix and a number a particle dispersed in the matrix and coated with the matrix, the component of the matrix is an alginate, and the particle is a medicament having a therapeutic effect on a peptic ulcer; and a capsule, a package Covering the surface of the microsphere, it consists of a chitosan. BRIEF DESCRIPTION OF THE DRAWINGS The above and other objects, features and advantages of the present invention will become more <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; As shown in Fig. 1, the pharmaceutical carrier for digestive ulcers of the present invention comprises a microsphere 1 and a coating 2, the coating 2 is coated on the surface of the microsphere 1 and the microsphere 1 comprises A matrix 11 and a plurality of particles 12 are dispersed in the matrix 11. Wherein, the matrix 11 of the microsphere 1 and the composition of the envelope 2 are preferably selected from a natural biodegradable material, which is charged under appropriate circumstances and can be produced by a metal ion curing agent. Colloidal coating ability; and the particles are

An agent that has a therapeutic effect on a peptic ulcer (such as an antacid, a proton pump inhibitor, etc.). The biodegradable material of the present invention refers to a polymer material such as alginate, chitosan or collagen (c〇llagen), which contains a hydrolyzable bond (such as an ester group). , guanamine or urea group, etc., can be decomposed into smaller molecules by the action of enzymes in biological individuals, and can be applied to the development of biomedical materials. It is more biocompatible than other synthetic biomedicines (4). The recording can be divided, which can be compared with the rate of reaction and possible toxicity of the body in the biological individual. Therefore, the drug carrier for the peptic ulcer of the present invention is safe. In this embodiment, the matrix u is a brown algae (five), the brown algae natural poly-polymer, soluble in a physiological solution (such as water) and: the browning can be combined with divalent cations The gelatin which produces a gelatin effect in the treatment of 'Xiehua Road Cancer', has a colloid which is formed by the bonding of the algae gel. The present invention can exist in the present invention, so that the form of the drug can be maintained in the stomach acid. Stabilizing the structure of algin glue = sustained release of the drug carrier of the cancer. The brown 201138788

:to.粒子 And the particle 12 is a proton pump inhibitor (ΡΡΙ) selected from the group consisting of omeprazole, lans〇praz〇ie, dexlansop face, angstrom A cluster of compounds such as es〇mepraz〇ie, pantoprazole (_〇praZ〇le) and rabera abepraz〇le (for related knots, please refer to the next phantom, the proton (IV) Inhibitors can selectively and specifically block the hydrogen/potassium triglyceride [H/K ATPase] enzymes of the gastric parietal cells to reduce gastric acid secretion* to achieve 2 digestive tract cancers ^^f ^ ^ In the brown algae bag of the reversal of the side, the shape of the microspheres is dispersed in the colloidal alginate to form the microspheres 1 and has a sustained release effect. This: ==Γ can be in the stomach The environment is re-extracted in the intestines, and it is gradually released in the intestines. It is smooth in the intestines: it is absorbed and acts to inhibit the secretion of gastric acid: ^ can ^ This invention - the secret of the digestive tract It has a relatively release effect, which can maintain a long sustained release time, so that the agent that has the therapeutic effect on the (4) slow-course ulcer can be more perfect === The proton pump Structure of the inhibitor: therapeutic effect. 201138788 omeprazole

Lansoprazole esomeprazole dexlansoprazole

Pantoprazole rabeprazole

The envelope 2 comprises a chitosan, which provides coating, mucosal adsorption and hemostatic effects of the microsphere 1. Wherein, the chitosan is one of the 201138788 listener molecules, and is positively charged under the acid ring), and the chitosan can be decomposed in the biological individual, and has antibacterial and biological effects; Chitosan is a cationic glycan molecule with mucosal adsorption, sustained permeability and hemostatic effect. Therefore, the chitosan can transfer drugs in a strong acid environment (such as the stomach environment) by its own cationic glycan molecule. More specifically, the envelope 2 of the present invention is positively charged due to its composition (chitosan), and can be coated on the surface of the negatively charged microsphere 1 (containing alginate) to form a coated state. The coating relationship between the envelope 2 and the microspheres 1 can strengthen and maintain the structure of the microspheres i, so that the drug carrier for the peptic ulcer of the present invention is less susceptible to damage during digestion, and affects The sustained release effect is exerted; in addition, the chitosan of the capsule 2 has the characteristics of mucosal adsorption and can stay in the digestive tract. Referring to Figures 2 and 3, the pharmaceutical carrier of the present invention is administered to a living body and then released in the stomach and the intestine respectively, wherein, according to Fig. 2, the pharmaceutical carrier is administered to the biological individual. At 24 hours, there was only a release rate of less than 20% in the stomach, and the release rate increased with time but remained at about 20 to 30% 80 hours after administration; and the drug carrier was in the intestine The release (Fig. 3) is 60% of the release rate 24 hours after the administration of the biological individual, and the release rate is relatively increased with time. The release rate after 80 hours of administration is nearly 1.0%. The result shows that the drug carrier for digestive tract cancer of the present invention can be protected from the destruction of gastric acid and maintain the carrier-coated configuration, and therefore has a good sustained-release effect, so that the coated agent can be smoothly performed. Slow release, absorption, and action in the intestine contribute to an increase in the effectiveness of the therapeutic agent. In addition, please refer to Figure 2 again, when it is proposed to invest in a biological individual 201138788

The invention relates to a pharmaceutical carrier for digestive ulcer, which can be retained in the stomach wall or the cells of the upper intestinal tract (such as the duodenum) by the mucus adsorption property of the chitosan component during the absorption process. Chitosan can exert hemostasis and antibacterial function, and has a direct therapeutic effect on the wound or ulceration of the stomach wall or upper intestinal tract. 'At the same time, the chitosan has permeability in the stomach (acidic soil)' It can penetrate the stomach wall to deliver the drug and directly act on the wound. Therefore, about 20~30% of the release rate can be observed in the stomach, which indicates that part of the drug carrier adheres, penetrates and releases to the gastric wall cells, and acts. Therefore, the drug carrier for digestive tract ulcer of the present invention can be attached to the digestive tract cells and exerts the effect of stopping bleeding and sterilizing directly in the affected part of the wound, which can improve the efficiency of treatment of the digestive tract ulcer. The chitosan structure:

As described above, the pharmaceutical carrier for digestive ulcers of the present invention contains alginate and chitosan, the stability of the alginate in an acidic environment, and the alginate and chitosan The drape effect, the stability of the drug depends on the turning of the environment, and the integrity of the coated agent is 'the sustained release effect of the drug' is better; and the chitin, the enzyme, the secret It has a special plant that is finer than the digestive tract and ▲, and stays and acts directly on the affected part, so that the therapeutic effect of the drug carrier on the digestive tract can be increased; in addition, the touch _ and several stalks become The biodegradable material 'is decomposable and non-toxic - 11387387' has better biocompatibility and safety. The above drug carrier for digestive ulcer can be prepared by a free drop: genus, emulsification method, spray method and electrospinning method, and the second embodiment: using the electrospinning method to carry out the drug carrier of the invention Preparation, 】 driving the substrate of the present invention (brown secret) to produce a colloidal coating of the particles to form the day; two: = 蓉 and the envelope (chitosan) to cover the microspherical cost of the steps, so that the Japanese The process of the drug carrier can be carried out and the particle size and uniformity of the music carrier can be prepared by the precise control of the electric field strength. Referring to Figures 4A and 4B, which is a schematic view of an electrospinning operation for digesting a drug carrier, the electrospinning operation of the present embodiment is 4% by weight of alginate (matrix). A solution of s-sub-inhibitor (particle) with a concentration of 1:1 as a concentration of 4 G mg/mL was systemized. Liquid 3; the mixed liquid 3 can be drawn by an electric field 4 and dropped into a solid solution. The solidified liquid 5 can be bonded to the solidified liquid 5 by a 25% divalent contact solution and 10% chitin (matrix). The price of liquid 3 of the brown algae is completed, and the one of the valences of the genus is produced by colloidal coating of butyl hydride inhibitors (particles) to form a number of particles, which are then coated by the curing solution 5 Covering the microparticles to obtain the $-body having a uniform particle size and regular shape (such as FIG. 4B), and the particle size range distribution of the drug carrier can be controlled by the adjustment of the rotation 'as shown in FIG. 5, the drug The micro-carrier of the carrier: plus the electric field strength and the distribution is 120~ measured in the stomach Π Π! In the digestive tract cancer, the drug is cut, because it contains brown algae, it can be stable and protects the proton pump inhibitor, and the chitin Glycan 201138788 tfS more butterfly turn brown turn good (four) inhibit (four) coating ° Hai drug carrier configuration 'has the effect of avoiding gastric acid damage and improving sustained release effect ^. &lt; The drug carrier for digestive tract ulcer of the present invention can absorb the mucosa of the digestive tract by containing a few butyl vinegar, and increase the time when the drug carrier stays in the digestive tract ^ ' directly penetrates the gambling layer to provide hemostasis to the affected part, and suppress And the role of protecting the wound, etc., has the effect of improving the therapeutic effect. The pharmaceutical carrier for digestive tract ulcer of the present invention is completely made of a biodegradable material, which has high biocompatibility, good biodegradability, low toxicity and easy to be evaluated in a biological individual, and has Use safety and reduce side effects. The present invention has been disclosed in the above-described preferred embodiments, and it is not intended to limit the invention. It is intended that the present invention may be practiced without departing from the spirit and scope of the invention. The technical scope of the invention is protected by the invention, and therefore the scope of the invention is defined by the scope of the appended claims. —13 — 201138788 [Simplified illustration] Fig. 1 is a schematic view of a pharmaceutical carrier for digestive ulcers of the present invention. Fig. 2 is a schematic view showing the gastric release of the drug carrier for digestive ulcers of the present invention. Fig. 3 is a schematic view showing the intestinal release of the pharmaceutical carrier for digestive ulcers of the present invention. Fig. 4a is a schematic view showing the electrospinning operation of the pharmaceutical carrier for digestive ulcers of the present invention. Figure 4b: Electrical representation of the electrospun pharmaceutical carrier of the present invention for use in peptic ulcers. Fig. 5 is a graph showing the relationship between the electric field strength of the electrophoresis method of the drug carrier for digestive ulcers and the particle size of the carrier. [Main component symbol description] [Invention] Lu 1 microsphere 11 matrix 12 particle 2 coating 3 mixed liquid 4 electric field, 5 solidified liquid — 14 —

Claims (1)

201138788 VII. Patent application garden: 1. A pharmaceutical carrier for peptic ulcer, comprising: a microsphere comprising a matrix and a plurality of particles dispersed in the matrix and coated by the matrix, the matrix The component is an alginate, and the particle is a medicament having a therapeutic effect on a peptic ulcer; and a capsule coated on the surface of the microsphere and shared by a chitosan composition. _ 2. A pharmaceutical carrier for digestive ulcers as described in claim 1 of the patent application, wherein the agent having a therapeutic effect on peptic ulcer is a proton pump inhibitor. 3. A pharmaceutical carrier for digestive ulcers according to item 2 of the patent application scope, wherein the proton pump inhibitor is selected from the group consisting of omeprazole, lansoprazole, and right blue. A group consisting of dexlansoprazole, esomepraz〇le, pantoprazole, and rabeprazole. ❿ 4. The drug carrier for digestive ulcers as described in claim 1 or 2 wherein the ratio of the matrix to the particles is 1:1. 5. The drug carrier for peptic ulcer according to claim 1 or 2, wherein the ratio of the chitosan to the matrix and the particles is 1:1. The drug for digestive tract ulcers according to claim 1 or 2, wherein the particle size range of the drug carrier is 120 to 1500 micrometers (//m) ° The drug dragon for digestive ulcer according to the above item 1 or 2, wherein the preparation method of the drug carrier is selected from the group consisting of a drip method, an emulsification method, and a spray method. —16 —