JPS6011893B2 - Immobilized medicine and its manufacturing method - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an immobilized drug and a method for producing the same.

In recent years, instead of being administered orally or by injection, it has become common practice to preliminarily immobilize medicines on a base material and then apply the immobilized medicines on the skin or embed them in the body. It has become to.

In particular, when it is necessary to continuously administer the drug into the body over a long period of time, such as in the case of contraceptives, it is advantageous to implant the immobilized drug into the body. Conventionally, silicone rubber has been used as a base material for immobilizing medicines to be implanted in the body.

Although this drug is excellent in terms of durability and non-toxicity to the human body, it is difficult to immobilize the medicine, and it is difficult to remove it from the body after the immobilized medicine is consumed. It becomes necessary to do so. The present inventors have completed the present invention as a result of intensive research to develop a substrate for fixing medicines that does not have the above-mentioned drawbacks.

That is, according to the present invention, in an amino acid copolymer molded product containing pendyl glutamate, at least a part of the pendyl glutamate residue contained therein is represented by the general formula (wherein R is an alkyl group). An immobilized drug is provided, characterized in that the drug is specifically immobilized on the substrate using a substrate substituted with a glutamine residue.

In the copolymer of pendyl glutamate and other amino acids such as leucine, alanine, and methionine used in the present invention, the molecular weight is usually about 20,000 to 500,000, and the proportion of glutamipendyl polyphosphate in the copolymer. is about 5 to 95 mol%.

In the present invention, in order to use this copolymer as a base material for fixing a drug, the copolymer is formed into an appropriate shape and then treated with hydroxyalkylamine.

In this case, the hydroxyalkylamine used is one represented by the general formula HO-R-NH2 (wherein R is an alkyl group having 1 to 8 carbon atoms).

In addition, as a treatment method, the molded product is immersed in hydroxyalkylamine at a temperature of 20 to 80 oo,
The following reaction may be carried out by bringing the two into sufficient contact. Through this treatment, at least a portion of the pendyl glutamate residues contained in the copolymer are replaced with glutamine residues represented by the general formula, and the copolymer is converted into an alcohol-swellable molded product. In this case, the substitution rate is at least 5 mol %, usually 5 to 10 mol %, based on the total pendyl glutamate residues.
It is 0 mol%. The shape of the copolymer molded product is arbitrary, such as a film, a pellet, or a rod. It should be noted that those without hydroxyalkylamine treatment have poor swelling properties in alcohol and water and are unsuitable as base materials.

In order to immobilize a drug on the base material obtained as described above, first, the base material is heated with alcohol or alcohol in order to make it easier to immobilize the drug using its alcohol swelling property. It is immersed in an aqueous solution and swelled.

In this case, by adding the drug in advance to alcohol or an alcohol aqueous solution and melting or dispersing it, it is possible to achieve specific immobilization of the drug at the same time as swelling of the molded product. The desired specific immobilization of the drug can also be achieved by immersing the swollen molded product in another solution containing the drug, such as an aqueous solution. The molded product with the drug immobilized in this way is dried, and an appropriate amount of alcohol or water (
Usually, drying treatment is carried out using heating or reduced pressure conditions as necessary so that the dry molded product has a concentration of 0 to 2% by weight).

As the alcohol used in the present invention, lower alcohols such as methanol, ethanol, and propyl alcohol are used. Further, the swelling ratio of the molded product is preferably in the range of 30 to 50% by weight based on alcohol or water content based on the dry molded product in order to preferably immobilize the drug. It should be noted that the term "medicine" as used in the present invention is interpreted in a broad sense and includes medicines for humans and animals, and also includes preventive medicines in addition to therapeutic medicines.

The amount of drug specifically immobilized on the base material is usually 30 to 30% in the product.
It is about 90% by weight. In the immobilized medicine of the present invention, since the amino acid copolymer containing pendyl glutamate used as the base material is hydrolyzable, even if it is buried in the body, it will be gradually hydrolyzed, and after a long period of time, It is broken down into amino acids including glutamic acid.

Therefore, after consumption of the medicine, there is no need to remove the base material from the body, and since the decomposed product is an amino acid, it also serves as a nutrient for the human body. Furthermore, the product of the present invention allows easy adjustment of the amount of water retained, and can also be used by applying it to the skin. Next, the present invention will be explained in more detail with reference to Examples.

Example o A film (0.1 thickness) formed from a copolymer of leucine and pendyl glutamate (molar ratio of leucine to pendyl glutamate G7:3) was placed in 3-aminopropanol at a temperature of 60°C. So, after soaking for 141 hours,
The surface was washed with ethanol and water.

Next, this film was soaked in alcohol at a temperature of 25°C, then pulled out, and then placed in ethanol containing a large excess of the drug (acetylsalicylic acid) dissolved at a temperature of 25°C.
After soaking for 2 hours at oo, it was dried at a temperature of 25°C.

The product thus obtained had the following properties. Ethanol content ・・・・・・・・・・・・・・・
・・0.2% drug fixation rate ……
...300% The ethanol content and drug immobilization rate mentioned above are both percentages by weight relative to the dry film.

Next, the immobilized medicine obtained above was soaked in water, and the total amount of medicine released (ratio of elution to the total amount of immobilized medicine) was measured.

The results are shown below. Time Amount shipped from port (hr) (%) 1 8 12 22 24 45 48 90 For comparison, we conducted an experiment using the same aircraft as above, except that 3-aminopropanol treatment was not performed. In some cases, molded products have poor swelling properties in alcohol and water (alcohol content of 5% or less, water volume of 1%).
(below), the amount of drug immobilized was only 5%.

Claims (1)

[Claims] 1. In an amino acid copolymer molded product containing benzyl glutamate, at least a portion of the benzyl glutamate residue contained therein is expressed by the general formula ▲ mathematical formula, chemical formula, table, etc. ▼ (in the formula, An immobilized drug characterized in that a drug substituted with a glutamine residue represented by (R is an alkyl group) is used as a base material, and a drug is supported and immobilized on the base material. 2. After contact-reacting an amino acid copolymer molded product containing benzyl glutamate with a hydroxyalkylamine represented by the general formula NH_2-R-OH (wherein R is an alkyl group), using alcohol or an aqueous alcohol solution. 1. A method for producing an immobilized drug, which comprises: swelling the swollen product, supporting and immobilizing the drug on the swollen product, and then drying.