TW201517919A - Drug support body with soluble separation layer - Google Patents

Abstract

Provided is a drug-bearing supporting medium which enables appropriate administration of a drug to an eye. This drug-bearing supporting medium for administrating a drug to an eye is provided with: a drug layer which comprises a drug and a water-soluble polymer; a dissolution separation layer which comprises a water-soluble polymer having water solubility higher than that of the water-soluble polymer of the drug layer; and a supporting body which functions as a handle. The drug layer and the supporting body are attached respectively on opposite sides of the dissolution separation layer.

Description

a support having a dissolution separation layer and a drug attached thereto

The present invention relates to a medicated support for administering a medicament to the eye.

Eyedrops have been widely known as ophthalmic agents since ancient times. In the case of an eye-dropping agent, when the liquid medicine contained in the eye-drop container is dropped, the amount of dripping is different depending on the pressure of the eye-drop container, and the desired dripping amount cannot be administered.

Further, a method of administering a certain amount of a drug to the eye is known to insert a solid composition for ophthalmology into the eye. In the solid composition, the essential chemical component to be administered once in one solid composition can be administered in a certain amount, but the solid composition cannot be maintained by hand by directly administering the solid composition.

An ophthalmic preparation for solving the above-described problems is disclosed in Patent Document 1 as an applicator for administering a pharmaceutical agent to a wet living body surface. In short, the applicator is provided with a base layer containing a pharmaceutical component in a soluble matrix on one end of an applicator having a long thin strip shape and discarded after use. Forming the base layer The separation portion having a thinner intermediate portion than the other portions (refer to Fig. 1 of Patent Document 1). Since the applicator contacts the living body surface of the administration site by holding the other end opposite to the drug body of the applicator by hand, the thinner separation portion is dissolved and the drug is made smaller than the other portions. Since the main body is separated from the applicator and administered to the main body of the drug, the sterilized state at the time of administration of the drug can be maintained, and a certain amount of the drug can be administered.

[Practical Technical Literature] [Patent Literature]

[Patent Document 1] Japanese Patent Publication No. 4-11229

However, when a base layer having no original thickness is formed as a thinner separation portion than other portions, processing is extremely difficult. Further, even if the separation portion can be formed, the difference between the solubility of the separation portion and the solubility of the other portion is insufficient. For example, the front end side is more easily separated from the separation portion in the base layer, and a certain amount of the drug cannot be administered.

The present invention has been made in view of the above circumstances, and provides a drug-attached support body capable of reliably administering a certain amount of a pharmaceutical agent to an eye.

The drug-attached support for administering the drug to the eye of the present invention comprises a drug layer containing a drug and a water-soluble polymer, and a water-soluble polymer having a water-soluble property set to be higher than the drug layer. Dissolved separation layer of a polymer, and There is a support that can be held by hand, and the aforementioned drug layer and the support are connected to the opposite side via a dissolution separation layer.

In the present configuration, the form of the drug layer and the dissolution separation layer is not particularly limited. For example, it is preferably a film-like shape, and when the support is in the form of a hand with a support for a drug, it can be used as a vaccine. The applicator for the drug. Further, the support of the present invention with a pharmaceutical agent can be administered while maintaining the sterilized state.

Further, the water solubility of the dissolution separation layer provided between the drug layer and the support is characterized by higher water solubility than the drug layer. Therefore, when the drug is administered, the drug layer is separated from the drug-attached support by dissolving the separation layer on the surface of the eye to dissolve faster than the drug layer, and is administered to the surface of the eye. As a result, a certain amount of the drug (drug layer) can be surely administered.

As described above, a drug-attached support capable of reliably administering a certain amount of a drug can be provided.

In the above configuration, it is preferred that all or part of the drug layer is partially overlapped with the above-mentioned dissolved separation layer.

By increasing the overlapping portion (contact area) of the drug layer and the dissolution separation layer, the connection strength between the drug layer and the dissolution separation layer can be increased.

Further, it is preferred that the dissolution separation layer and the support are partially overlapped.

By overlapping the drug layer, the dissolution separation layer, and the dissolution separation layer and the support, the drug layer, the dissolution separation layer, and the support can be integrated to increase the connection strength.

In the above configuration, it is preferable that the drug layer, the dissolution separation layer, the dissolution separation layer, and the support are reliably joined by heat fusion or adhesion.

In the above configuration, the average collapse time of the dissolution separation layer (the time required for disintegration of the film-form substrate having a predetermined size in water or physiological saline) is 60 seconds or less, preferably 50 seconds. the following. This is because the average collapse time of the dissolved separation layer exceeds 60 seconds, which may result in an excessively long time required to administer the drug to the eye using the drug-attached support.

According to this configuration, since the dissolved separation layer dissolves rapidly on the surface of the eye, a certain amount of the drug can be quickly administered to the surface of the eye.

1‧‧‧Support with pharmacy

2‧‧‧ drug layer

3‧‧‧Support

4‧‧‧Dissolved separation layer

[Fig. 1] is a side view showing an example of a support with a drug of the present invention.

[Fig. 2] Fig. 2 is a top view showing an example of a support with a drug of the present invention.

[Fig. 3] is a view showing a state of use of a drug-attached support.

Fig. 4 is a side view showing a drug-attached support according to another embodiment of the present invention.

Fig. 5 is a side view showing a drug-attached support according to another embodiment of the present invention.

Fig. 6 is a side view showing a drug-attached support according to another embodiment of the present invention.

[Fig. 7] showing a medicinal agent according to another embodiment of the present invention Side view of the support.

[Fig. 8] Fig. 8 is a side view showing a drug-attached support according to another embodiment of the present invention.

[Fig. 9] Fig. 9 is a side view showing a drug-attached support according to another embodiment of the present invention.

[In order to implement the invention]

In the following, an embodiment of the drug-attached support 1 of the present invention will be described based on the drawings. However, it is not limited to the following embodiments, and various changes can be made without departing from the spirit and scope of the invention.

As shown in Fig. 1, the drug-attached support 1 is composed of a film-formed drug layer 2, a film-like dissolving and separating layer 4, and a support body 3 which can be held by hand. The size of the drug layer 2 is not particularly limited, and is preferably, for example, about 1 to 4 mm in width, 5 to 10 mm in length, and 1 to 300 μm in thickness; and the size of the dissolving and separating layer 4 is not particularly limited, for example, about 1 to 4 mm in width. Further, the length is about 3 to 10 mm, and the thickness is preferably 1 to 300 μm. Further, the size of the support 3 is not particularly limited, and is preferably, for example, about 1 to 4 mm in width, about 10 to 60 mm in length, and 50 to 2 mm in thickness.

The support 3 has, for example, a rectangular shape that is long and thin, and is formed into a form that can be held by hand when the sterilization state is maintained. The material of the support 3 is not particularly limited, and paper, plastic, aluminum foil, or the like can be suitably used. Further, the plurality of layers may be laminated to form the support 3.

As shown in Fig. 1 and Fig. 2, the phase is dissolved in the separation layer 4 The drug layer 2 and the support 3 are connected to the opposite sides, and the dissolution separation layer 4 is provided between the drug layer 2 and the support 3. More specifically, the drug layer 2 and the dissolving and separating layer 4 are each a film-like substrate, which is bonded to the lower portion of the entire drug layer 2 and a portion above the dissolving and separating layer 4, and is melted or bonded by heat. The lower portion of the partially dissolved separation layer 4 is connected to the upper portion of the support body 3. Thus, the connection strength can be increased by overlapping the drug layer 2 and the dissolution separation layer 4, and dissolving the separation layer 4 and the support 3, and increasing the contact areas.

Further, the method of connecting the drug layer 2 to the dissolution separation layer 4 and the method of connecting the dissolution separation layer 4 and the support 3 may be connected by a method other than hot press welding or adhesion.

The drug layer 2 is composed of a matrix containing a water-soluble polymer and a drug, and may be blended with an emulsifier such as Polysolbate 80 or a plasticizer such as glycerin in the matrix, or may be mixed at the same time. Two or more kinds of water-soluble polymers or a matrix of two or more layers.

The dissolving and separating layer 4 is composed of a matrix containing a water-soluble polymer containing no drug, and an emulsifier or a plasticizer may be blended in the matrix as needed, and in addition, in order to further improve water solubility, A water-soluble polymer having a small molecular weight such as a sugar alcohol or oligomer such as mannitol or a dendrimer is added, and bubbles are simultaneously introduced. Two or more kinds of water-soluble polymers may be mixed as needed. The base constituting the dissolution separation layer 4 can be set in such a manner that the water solubility is higher than that of the substrate constituting the drug layer 2. Thus, by dissolving the water-soluble layer of the dissolving and separating layer 4 higher than that of the drug layer 2, it is in contact with the tear liquid at the time of administration, and the dissolving and separating layer 4 dissolves faster than the drug layer 2. And by setting The dissolution separation layer 4 having a higher water solubility than the drug layer 2 does not cause a problem that the drug amount 2 is separated from the middle portion during administration, and the drug layer 2 is separated from the drug-attached support 1 and adheres to the eye. Since the surface is fixed, a certain amount of the drug can be reliably administered (see Figs. 1 to 3).

The index indicating the water solubility can be an average collapse time for water or physiological saline when a film-form substrate having a certain size [2 × 7 mm and a film thickness of about 30 μm] as described in the examples is used. For example, the average collapse time of the substrate constituting the drug layer 2 is not particularly limited, and is preferably 100 minutes or shorter.

Further, the average collapse time of the film-form substrate constituting the dissolution separation layer 4 is more soluble in water or physiological saline, and the dissolution of the separation layer 4 is more easily dissolved by the tear liquid on the surface of the eye. A special limitation is preferably 60 seconds or less, and more preferably 50 seconds or less. When the average collapse time of the dissolution separation layer 4 exceeds 60 seconds, the time required for administering the drug to the eye is too long by using the drug-attached support 1. In other words, by setting the average collapse time of the dissolution separation layer 4 to 60 seconds or less, the dissolution separation layer 4 can be quickly dissolved in the tear liquid on the surface of the eye, and a certain amount of the drug is rapidly administered to the surface of the eye.

The average collapse time of the film-form substrate constituting the drug layer 2 is longer than the average chipping time of the film-form substrate constituting the dissolution separation layer 4, and the difference is not particularly limited, and is preferably 1 second or more, more preferably It is more than 2 seconds. In short, by setting the difference in the average collapse time to the above range, the dissolution separation layer 4 dissolves on the surface of the eye faster than the drug layer 2 at the time of administration, and the drug layer 2 can be self-supported with the drug support 1 Separate and give to the eye surface. Further, when the drug layer 2 and the partial dissolution separation layer 4 are laminated, the total amount of the collapse time of the drug layer 2 and the average collapse time of the dissolution separation layer 4 is set to be larger than that of the dissolution separation layer 4. The average collapse time is larger (more preferably, it is a large value of 2 seconds or more), and the dissolution separation layer 4 can be dissolved on the surface of the eye more quickly than the laminate of the drug layer 2 and the dissolution separation layer 4.

In view of the above problems, the substrate constituting the drug layer 2 is not particularly limited as long as it is a water-soluble matrix, and is, for example, a cellulose-based water-soluble polymer, an acrylate-based polymer, a polyvinylpyrrolidone, a polyvinyl alcohol, or a poly (Ethylene oxide), polysaccharides, etc., specifically, CMC DIACEL 1205 (average collapse time 10 seconds, manufactured by DIACEL FINECHEM), PLASDONE K-90 (average failure time 11 seconds, manufactured by ASHLAND), HPL -C (average collapse time: 27 seconds, manufactured by Nippon Soda Co., Ltd.), GOHSENOL EG-05 (mean collapse time: 29 seconds, manufactured by Nippon Synthetic Chemical Co., Ltd.), TC-5S (average collapse time: 34 seconds, manufactured by Shin-Etsu Chemical Co., Ltd.) ), METOLOS 60SH-50 (average collapse time: 43 seconds, manufactured by Shin-Etsu Chemical Co., Ltd.), METOLOS SM15 (average collapse time: 138 seconds, manufactured by Shin-Etsu Chemical Co., Ltd.), METOLOS SM100 (average collapse time: 162 seconds, manufactured by Shin-Etsu Chemical Co., Ltd.) ), CELNY M (average collapse time 287 seconds, manufactured by Japan Soda Co., Ltd.), KIMICA ALGIN IL-2 (average collapse time 332 seconds, manufactured by KIMICA), HEC DIACEL SE400 (average collapse time 1800 seconds or more, DIACEL FINECHEM) Water soluble in company system) Preferred polymers.

Further, the matrix constituting the dissolution separation layer 4, for example, cellulose-based water-soluble Polymer, polyvinylpyrrolidone, polyvinyl alcohol, etc., specifically, including CMC DIACEL 1205 (average collapse time 10 seconds, manufactured by DIACEL FINECHEM), PLASDONE K-90 (average collapse time 11 seconds) , ASHLAND company), HPL-C (average collapse time 27 seconds, manufactured by Japan Soda Co., Ltd.), GOHSENOL EG-05 (mean collapse time 29 seconds, manufactured by Nippon Synthetic Chemical Co., Ltd.), TC-5S (average collapse time) It is preferable to use a polymer having a high water solubility such as a METOLOS 60SH-50 (average collapse time of 43 seconds, manufactured by Shin-Etsu Chemical Co., Ltd.) for 34 seconds.

The combination of the substrate constituting the drug layer 2 and the substrate constituting the dissolution separation layer 4 is not particularly limited, and the substrate constituting the drug layer 2 contains, for example, a water-soluble polymer such as HPC-L or METOLOS SM15, and further, a dissolution separation layer 4 is formed. The water-soluble polymer having a higher water solubility such as PLASDONE K-90 or CMC DIACEL 1205 is preferred.

Next, a method of using the drug-attached support 1 will be described. The administration of the drug layer 2 to the surface of the eye will be described as an example, for example, administration of the anterior eye portion such as the orbital conjunctiva or the conjunctival sac. As shown in Fig. 3, the user holds the vicinity of the end of the support 3 on the side opposite to the end on which the drug layer 2 is provided on the side of the drug-attached support 1 with the finger, so that the drug layer 2 is brought close to the administration. Part. In the present embodiment, the lower eyelid is pulled down with one hand to expose the conjunctiva, and at the same time, the vicinity of the end portion on the side opposite to the side on which the drug layer 2 is provided on the support 3 is held by the finger of the other hand, so that the drug layer 2 and The dissolving separation layer 4 is close to the surface of the eye and contacts the exposed conjunctiva. At this time, since the water solubility of the dissolving and separating layer 4 is larger than that of the drug layer, the dissolving and separating layer 4 is dissolved in tear fluid, and as a result, the drug is dissolved. The agent layer 2 is quickly separated from the support 3 and attached to the surface of the eye. The drug-attached support 1 is not partially separated in the middle of the drug layer 2, and a certain amount of the drug (drug layer 2) can be reliably administered.

(Another embodiment)

Another embodiment of the drug-attached support 1 of the present invention is shown in Figs. 4 to 9 . Fig. 4 shows that the lower portion of the drug layer 2 is connected to the upper portion of the partially dissolved separation layer 4, and the lower portion of the partially dissolved separation layer 4 is connected to the upper portion of the support member 3. Fig. 5 shows that the lower portion of the entire drug layer 2 is connected to the upper portion of the partially dissolved separation layer 4, and the upper portion of the partial dissolution separation layer 4 is connected to the lower portion of the support member 3. Fig. 6 shows that the lower portion of the drug layer 2 is connected to the upper portion of the partially dissolved separation layer 4, and the upper portion of the partially dissolved separation layer 4 is connected to the lower portion of the support member 3. Fig. 7 shows that the lower portion of the entire drug layer 2 is connected to the upper portion of the dissolved separation layer 4, and is connected so as not to overlap the upper and lower sides of the dissolution separation layer 4 and the upper and lower sides of the support 3. Fig. 8 shows the manner in which the drug layer 2, the dissolving and separating layer 4, and the support 3 are not overlapped. Fig. 9 shows a form in which the lower portion of the entire drug layer 2 is connected to the upper portion of the dissolved separation layer 4, and the dissolution separation layer 4 is sandwiched between the two supports 3. In Fig. 9, the support 3 and the dissolving and separating layer 4 do not have to be subjected to hot press welding or bonding.

[Examples] (1) Method for measuring average collapse time of film-like substrate and measurement result

CMC DIACEL 1205 [Polymer A] 18.0% (w/w) as a water-soluble polymer, glycerol 1.62% (w/w) as a plasticizer, POLYSORBATE 80 0.09% (w/w as an emulsifier) In a manner, a water-soluble polymer (CMC DIACEL 1205), a plasticizer (glycerol), and an emulsifier (POLYSORBATE 80) were dissolved in a solvent (water) to prepare a sample 1. In addition, the same operation was carried out, as a water-soluble polymer, PLASDONE K-90 [Polymer B], HPC-L [Polymer C], GOHSENOL EG-05 [Polymer D], TC-5S [Polymer E ], METOLOS 60SH-50 [Polymer F], METOLOS SM15 [Polymer G], METOLOS SM100 [Polymer H], CELNY M [Polymer I], KIMICA ALGIN IL-2 [Polymer J] and HEC DIACEL SE400 [Polymer K] is dissolved in a solvent (water, ethanol, a mixture of water and ethanol), and, depending on the necessity, glycerol as a plasticizer and POLYSORBATE 80 as an emulsifier can be added as shown in Table 1. , making samples 2~11. Then, on the substrate of the polypropylene film, the samples 1 to 11 were coated with a thickness of about 30 μm using an applicator, and dried with warm air. Next, the obtained film-form substrate was finely cut into a size of 2 × 7 mm, and immersed in 10 mL of physiological saline at room temperature, and the collapse time of the film-form substrate was measured [the time until the matrix was completely dissolved until disappearance) ]. The results are shown in Table 1. Further, the average collapse time of each of the film-form substrates obtained from the samples 1 to 11 was measured by the average value of the collapse time of three times.

(2) Production with support

Using fluorescein sodium 10% (w/w) as a substitute agent, fluorescein sodium was added to each sample [sample 1, 3, 6, 7, 10, 11] to prepare a coating liquid for a drug layer. The coating liquid for a drug layer was applied onto a substrate of a polypropylene film by a coater at a thickness of about 30 μm and a width of 7 mm, and dried with a warm air. Then, the coating liquid for the dissolution separation layer was applied to the coating layer on the substrate to which the coating layer was applied, using a coater having a thickness of about 30 μm and a width of about 50 mm (samples 1, 2, 6, 10, 11). And forming a dissolved separation layer on the drug layer and drying it with warm air to obtain each laminated film. After separating the laminated films from the substrate and connecting the laminated film and the support (separation paper) with an adhesive, the obtained drug-attached support was finely cut into a size of 2 × 50 mm. Table 2 shows the types of water-soluble polymers constituting the respective drug layers or the respective dissolution separation layers of Examples 1 to 4 and Comparative Examples 1 and 2, or the average collapse time thereof.

(3) Trial application using rabbit eyes

In the center of the lower eyelid conjunctiva of the right eye of the normal rabbit ( ♂ , Japanese white, KITAYAMA LABES), the side of the dissolution separation layer of each of the drug-containing support prepared in the above (2) was attached for 10 seconds, and then recovered and visually observed. It is judged whether or not the entire amount of the drug layer can be administered to the conjunctival portion of the rabbit. When the total amount of the drug is administered to the conjunctival portion of the rabbit, it is "1", and when the total amount of the drug layer cannot be administered, or when only a part of the drug layer cannot be administered, it is "0", and the total value when the operation is repeated three times is calculated. The results are shown in Table 2. Further, in Examples 1 and 2, the drug-attached support in the form shown in Fig. 1 above the entire drug layer 2 and above the partially dissolved separation layer 4 was connected, and Examples 3 to 4 and comparison were carried out. Examples 1 to 2 are drug-attached supports in the form shown in Fig. 4 above the drug layer 2 of the connecting portion and the portion above the dissolution separation 4.

The drug-attached support of Examples 1 to 4 was separated from the support within 10 seconds, and the whole amount of the drug layer was administered to the conjunctival portion of the rabbit.

However, when the drug-attached support of the present invention is used, a certain amount of the drug can be surely administered to the eye.

[Industry use value]

The present invention is suitable for use in administering a pharmaceutical agent to a drug-attached support of the eye.

1‧‧‧Support with pharmacy

2‧‧‧ drug layer

3‧‧‧Support

4‧‧‧Dissolved separation layer

Claims (6)

A drug-attached support for administering an agent to an eye, comprising a drug layer containing a drug and a water-soluble polymer, and a water-soluble polymer having a water-soluble polymer set to be higher than the drug layer The material dissolves the separation layer and the support for holding the hand, and the drug layer and the support are connected to the opposite side via the dissolution separation layer. The drug-attached support of claim 1 which overlaps all or part of the aforementioned drug layer and a portion of the aforementioned dissolution separation layer. A support for a drug as claimed in claim 2, which is an overlapping portion of the aforementioned dissolution separation layer and a part of the aforementioned support. The drug-attached support according to any one of claims 1 to 3, wherein the aforementioned dissolution separation layer and the aforementioned support are heat-compressed or followed. The drug-attached support according to any one of claims 1 to 4, wherein the dissolution separation layer has an average collapse time of water or physiological saline of 60 seconds or less. A method of administering a medicament by administering a dose-providing agent to a surface of the eye using a drug-attached support according to any one of claims 1 to 5.