CN212067227U - A kind of gastric retention long-acting preparation - Google Patents

Abstract

The utility model provides a long-acting preparation retained in the stomach, which comprises a gastric soluble capsule shell and a medicine release unit, wherein the medicine release unit is folded into a geometric shape and is arranged in the gastric soluble capsule shell, the medicine release unit comprises a long and thin component and a biodegradable connecting piece, two ends of the long and thin component are sealed, at least one medicine release hole is arranged on the pipe wall, and the medicine is arranged in the long and thin component; the biodegradable connector is used to connect two ends of the elongated member. The preparation method of the utility model is simple, the long-acting preparation detained in the stomach releases the drug at a steady rate, adjusts the release rate and the release time of the drug by arranging the drug release holes with different quantities and diameters on the slender component, and controls the detention time of the preparation in the stomach through the degradation time of the biodegradable connecting piece.

Description

A kind of gastric retention long-acting preparation

technical field

The utility model relates to an oral sustained and controlled release preparation, in particular to a gastric retention long-acting preparation.

Background technique

Oral sustained-release preparations can maintain effective blood drug concentrations within 12-24 hours, which to a certain extent compensates for the strong first-pass effect, inaccurate positioning, high blood concentration fluctuations and poor patient tolerance of traditional oral preparations. Insufficient, improve the bioavailability of the drug. However, due to the interference of factors such as gastric emptying, gastric motility and gastric contents, most oral preparations are not fully absorbed in the gastrointestinal tract and have low bioavailability.

The research and development of gastroretentive preparations provides a more effective route of administration for the treatment of gastrointestinal diseases, and also provides a new treatment method for it. Gastric retention drug delivery system refers to a drug delivery system that can be retained in gastric juice after oral administration, prolong the release time of the drug in the digestive tract, and improve drug absorption. The system can promote the absorption of weakly acidic drugs in specific parts of the gastrointestinal tract. The absorption of certain drugs, drugs that are actively transported in the duodenum, drugs that are unstable in the intestinal environment, and drugs with a narrow therapeutic window can make up for the shortcoming of the short biological half-life of drugs.

At present, the commercially available long-acting gastric retention preparations mainly include gastric floating preparations, gastric sedimentation preparations, gastric adhesion preparations and gastric retention expansion preparations. The gastric flotation preparation enters the stomach after oral administration, and is in a floating state because the density is lower than that of gastric juice and its contents (1.004～1.010g·cm ^-3 ), and is not affected by gastric emptying, thereby prolonging the residence time of the drug in the stomach and achieving a long-term effect. . High-density pharmaceutical excipients are added to the gastric sedimentation preparation to make the total density greater than the density of the stomach contents. After oral administration, it will sink to the fundus of the stomach quickly, and the folds in the stomach will firmly wrap the drug and not be discharged, thereby The release time of the drug in the stomach is prolonged, but it cannot resist the physiological movement of the stomach. After the polymer adhesive material containing the drug in the gastric adhesive preparation contacts the gastric mucosa, under the comprehensive action of mechanical binding force, hydrogen bond, van der Waals force, electrostatic attraction, covalent bond, hydrophobic bond, etc. However, gastric adhesive preparations, especially bioadhesive preparations, are affected by gastric acid and mucus due to their characteristics. Gastric retention expansion preparations have a small volume when taken orally, but expand immediately after being swallowed into the stomach, and the volume becomes large enough to resist its discharge into the duodenum through the pylorus. It is mainly achieved by using some excipients that expand rapidly after water absorption, The preparation can be gradually eroded and safely excreted after the drug release is completed, but the complete expansion of the preparation cannot be completely completed before gastric emptying.

To sum up, gastric retention long-acting preparations also have their own limitations. They are still greatly affected by food and gastric emptying, the production process is complex, the drug encapsulation efficiency is not high, and toxic organic solvents are likely to remain. Large-scale mass production is difficult to meet the requirements of stability and reliability; some drugs cannot be uniformly released, and cannot achieve sustained and controlled release effects; at the same time, the preparations generally stay in the stomach for only 5-6 hours, which is a short time. Therefore, there is a need to develop novel gastric-retentive long-acting formulations.

Utility model content

The purpose of the utility model is to provide a gastric retention long-acting preparation, so as to solve the problems of short residence time of the existing gastric retention long-acting drug administration preparation, inability to release medicine uniformly, and complicated production process.

The purpose of this utility model is achieved in this way:

A gastric retention long-acting preparation, comprising a gastrosoluble capsule shell and a drug release unit, the drug release unit is folded into a geometric shape and arranged in the gastrosoluble capsule shell, the drug release unit includes an elongated member and a bioavailable A degradable connector, both ends of the elongated member are closed, and at least one drug release hole is opened on the tube wall, and a drug is arranged in the inside thereof; the biodegradable connector is used to connect the two ends of the elongated member .

Optionally, the elongated member is a silicone rubber tube, preferably a medical sterile silicone tube; preferably, the inner diameter of the silicone tube is 1-5 mm; preferably, the outer diameter of the silicone tube is 1.5-8 mm ; Preferably, the length of the silicone tube is 5.0~20.0cm.

Preferably, the diameter and number of the drug release holes on the tube wall of the elongated member can be determined according to the time and rate of drug release; A drug hole, leaving a section of non-porous tube wall at both ends of the elongated member to close the two ends of the elongated member and connect with the biodegradable connector; preferably, the diameter of the drug release hole is 0.2 mm~0.8mm; preferably, the number of the drug release holes is 1~10.

Specifically, the inner diameter of the longitudinal section of the silicone tube is 2 mm, the outer diameter is 3 mm, and the length is 9 cm. The glue with good sealing effect) is closed, and a hole is opened on one side of the silicone tube wall, with a diameter of 0.4mm~0.8mm, and the opening position is selected between 0.5cm and 8.5cm. The number is 7 to 10.

The biodegradable connector is a degradable suture, and the degradation time can be determined according to the drug release time, preferably 3 to 14 days.

Preferably, the drug is a sustained-release drug, which is made of drug-carrying and sustained-release auxiliary materials.

The drug loading is not particularly limited to its efficacy, as long as it is an active ingredient that can be administered orally; the active ingredient can be a gastrointestinal drug, a chemotherapeutic drug, a bronchodilator, a cardiotonic, an antihypertensive drug, a vasodilator, a vasoconstrictor Drugs, vascular enhancers, antipyretic, analgesic and anti-inflammatory drugs, hyperlipidemia drugs, antipsychotics, antibiotics, anti-epileptic drugs, anti-Parkinsonian drugs, antihistamines, anti-anxiety drugs, osteoporosis drugs, Skeletal muscle relaxants, hypnotic sedatives, antidiarrheal drugs, peptic ulcer drugs, autonomic nerve drugs, psychoneurotic drugs, antacids, intestinal regulating drugs, antitussive expectorants, antispasmodics, gout treatment drugs, diabetes drugs, Arrhythmia drugs, hormone drugs, and diuretics. As active ingredients, supplements such as vitamins and amino acids, or nutritional ingredients can also be used. These drug carriers can be used alone or in combination of two or more.

The sustained-release auxiliary materials can be selected from hydrophilic gel skeleton materials, such as K100M, hydroxyethyl cellulose, hypromellose, carbomer, sodium alginate, methyl cellulose, sodium carboxymethyl cellulose, and the like.

A preparation method of gastric retention long-acting preparation, comprising the following steps:

(a) opening at least one drug release hole on the tube wall of the elongated member;

(b) filling the inside of the elongated member with the drug, and closing both ends of the elongated member;

(c) Connect the biodegradable connector with the two ends of the elongated member, fold it into a geometric shape, and then fill it into the stomach-dissolving capsule shell.

Optionally, the drug is a sustained-release drug microtablet, which is made by adding the drug-carrying and sustained-release auxiliary materials into a suitable solvent (water or ethanol of different concentrations), and then using a special mold to press it into a tube suitable for the inner diameter of the elongated member. microtablets to fill the sustained-release drug microtablets into the interior of the elongated member.

In the utility model, a drug releasing unit folded into a geometric shape is arranged in the stomach-dissolving capsule shell, and when the capsule shell is dissolved in the stomach, the elongated member in the drug-releasing unit expands to form a ring shape, which cannot pass through the gastric pylorus, thereby realizing intragastric At the same time, the release rate and release time of the drug are adjusted by setting different numbers and diameters of drug release holes on the elongated member. The biodegradable connector can gradually degrade in the stomach over time, and the elongated member forms a linear tube. After that, it can be excreted smoothly, and the residence time of the preparation in the stomach is controlled by the degradation time of the biodegradable connector.

The gastric retention long-acting preparation of the utility model has stable drug release rate, convenient clinical administration, avoids one or several daily administrations, and is especially suitable for the elderly, children, and patients with swallowing difficulties or resistance to taking medicines. Improves medication compliance of patients, has fast onset of action and high bioavailability, and solves the shortcomings of current commercially available ordinary tablets in clinical application, and the preparation method is simple, the production process is easy to control, the quality is stable and reliable, and the drug encapsulation efficiency High, no toxic and harmful substances, suitable for mass production.

Description of drawings

Figure 1 is a schematic diagram of the structure of the drug release unit in the gastric retention long-acting preparation.

Figure 2 is a schematic diagram of the structure of the drug-releasing unit in the gastric retention long-acting preparation after unfolding.

In the figure, 1. Medical sterile silicone tube, 2. Drug filling section, 3. Drug release hole, 4. Sealing section, 5. Biodegradable connector.

3 is a graph of the daily release curve (a) and the cumulative release curve (b) of the huperzine A gastric retention long-acting preparation prepared in Example 2.

4 is the daily release curve (a) and the cumulative release curve (b) of the huperzine A gastric retention long-acting preparation prepared in Example 5.

FIG. 5 is an endoscopic photograph of the gastric retention long-acting preparation prepared in Example 6 in the stomach of a dog.

FIG. 6 is an X-ray photograph of the gastric retention long-acting preparation prepared in Example 6 in the stomach of a dog.

Detailed ways

The present invention will be further elaborated below in conjunction with the examples, and the following examples are only for illustration and do not limit the protection scope of the present invention in any way.

The processes and methods not described in detail in the following examples are conventional methods well known in the art. The reagents used in the examples are all analytically pure or chemically pure, and can be purchased commercially or prepared by methods well known to those of ordinary skill in the art. The following embodiments all achieve the purpose of the present utility model.

Example 1

Weigh 4 mg of Huperzine A and 1.5 g of hydroxypropyl methylcellulose K100M, take 0.5 ml of 75% ethanol to dissolve Huperzine A, evenly pour it into K100M, and mix thoroughly to obtain a soft material; use a special mold to press It was prepared into slow-release drug microtablets with a diameter of 1.9 mm, and dried for later use.

Take a medical sterile silicone tube with a length of 9cm (the inner diameter of the longitudinal section is 2mm, the outer diameter is 3mm), and one side of the tube wall is opened with a hole diameter of 0.5mm, and the hole is evenly opened between the 0.5cm to 8.5cm section of the silicone tube 7; fill the sustained-release drug microtablets in the 0.5cm to 8.5cm section of the open-hole silicone tube, and seal the empty sections 0.5cm away from each end by filling with a special silicone rubber adhesive; suture the sealed silicone section with degradable sutures, A closed drug-containing silica gel ring is formed, and the silica gel ring is folded and then filled into the stomach-dissolving capsule shell to obtain a long-acting preparation for gastric retention.

Example 2

The gastric retention long-acting preparation containing 4 mg of Huperzine A was prepared according to the method of Example 1, and the obtained gastric retention long-acting preparation was placed in a glass bottle, 10 ml of water was added, and the bottle was sealed, and 6 groups were performed in parallel. Put it into a shaker, the shaker speed is 75r/min, the absorbance value is measured by UV every day, and then the water is changed by 10ml, and it is continued to be put into the shaker for 15 days. The daily measurement data were recorded, averaged, and the daily release and cumulative release curves were drawn. The results are shown in Figure 3.

Example 3

Weigh 4 mg of Huperzine A and 1.5 g of hypromellose K100M, take 0.5 ml of 75% ethanol to dissolve Huperzine A, evenly pour it into K100M, and mix thoroughly to obtain a soft material; use a special mold Compressed into sustained-release drug microtablets with a diameter of 1.9 mm, and dried for later use.

Take a medical sterile silicone tube with a length of 9cm (the inner diameter of the longitudinal section is 2mm, the outer diameter is 3mm), and one side of the tube wall is opened with a hole diameter of 0.5mm, and the hole is evenly opened between the 0.5cm to 8.5cm section of the silicone tube 9; fill the 0.5cm to 8.5cm section of the open-hole silicone tube with sustained-release drug microtablets, and seal the empty sections 0.5cm away from each end by filling with a special silicone rubber adhesive; suture the sealed silicone section with degradable sutures, A closed drug-containing silica gel ring is formed, and the silica gel ring is folded and then filled into the stomach-dissolving capsule shell to obtain a long-acting preparation for gastric retention.

Example 4

Weigh 60 mg of tamsulosin hydrochloride and 1.5 g of hydroxypropyl methylcellulose K100M, take 0.5 ml of 75% ethanol to dissolve tamsulosin hydrochloride, evenly pour it into K100M, and mix thoroughly to obtain a soft material; The special mold is pressed into sustained-release drug microtablets with a diameter of 1.9mm, and dried for later use.

Take a medical sterile silicone tube with a length of 9cm (the inner diameter of the longitudinal section is 2mm, the outer diameter is 3mm), and one side of the tube wall is opened with a hole diameter of 0.5mm, and the hole is evenly opened between the 0.5cm to 8.5cm section of the silicone tube 9; fill the 0.5cm to 8.5cm section of the open-hole silicone tube with sustained-release drug microtablets, and seal the empty sections 0.5cm away from each end by filling with a special silicone rubber adhesive; suture the sealed silicone section with degradable sutures, A closed drug-containing silica gel ring is formed, and the silica gel ring is folded and then filled into the stomach-dissolving capsule shell to obtain a long-acting preparation for gastric retention.

Example 5

The gastric retention long-acting preparation containing 3 mg of tamsulosin hydrochloride was prepared according to the method of Example 4, the obtained gastric retention long-acting preparation was put into a glass bottle, 10 ml of water was added, and the stopper was sealed, and 6 groups were performed in parallel. Put it into a shaker, the shaker speed is 75r/min, the absorbance value is measured by UV every day, and then the water is changed by 10ml, and it is continued to be put into the shaker for 15 days. The daily measurement data were recorded, averaged, and the daily release and cumulative release curves were drawn. The results are shown in Figure 4.

Example 6

To determine that the formulation achieves gastric retention, barium sulfate (20 wt%) was used in place of the drug in the gastric retention formulation and they were administered to dogs that were fasted for one day. The dogs were placed in the prone position for the imaging procedure, and the intragastric state of the formulation was photographed using an endoscope to further confirm the gastric retention effect of the formulation. Figures 5 and 6 show the endoscopic pictures and X-ray pictures of the obtained gastric-retaining long-acting preparation in the stomach of dogs.

Claims (8)

1. The long-acting preparation is characterized by comprising a gastric soluble capsule shell and a medicine release unit, wherein the medicine release unit is folded into a geometric shape and is arranged in the gastric soluble capsule shell, the medicine release unit comprises a long and thin member and a biodegradable connecting piece, two ends of the long and thin member are closed, at least one medicine release hole is formed in the wall of the tube, and medicines are arranged in the long and thin member; the biodegradable connector is used for connecting two ends of the elongated member.

2. The gastro-retentive, long-acting formulation of claim 1, wherein the elongate member is a medical sterile silicone tube.

3. The long-acting preparation retained in the stomach according to claim 2, wherein the silicone tube has an inner diameter of 1 to 5mm, an outer diameter of 1.5 to 8mm, and a length of 5.0 to 20.0 cm.

4. The gastro-retentive, long-acting formulation of claim 1, wherein the elongated member has a drug release hole formed in one side of the wall of the elongated member and a non-perforated wall is left at each end of the elongated member to close the ends of the elongated member and to connect to the biodegradable connector.

5. The long-acting preparation retained in the stomach according to claim 1, wherein the diameter of the drug release hole is 0.2mm to 0.8mm, and the number of the drug release holes is 1 to 10.

6. The long-acting preparation retained in the stomach according to claim 2, wherein the inner diameter of the longitudinal section of the silicone tube is 2mm, the outer diameter is 3mm, the length is 9cm, the two ends of the silicone tube are closed, one side of the wall of the silicone tube is provided with an opening, the diameter of the opening is 0.4 mm-0.8 mm, the position of the opening is 0.5 cm-8.5 cm, and the number of the drug release holes is 7-10.

7. The gastro-retentive, depot formulation of claim 1, wherein the biodegradable connector is a degradable suture.

8. The gastro-retentive, long-acting formulation of claim 7, wherein the degradable suture has a degradation time of 3 to 14 days.

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