JP6334181B2 - Drug-supported substrate with dissolution separation layer - Google Patents

Description

  The present invention relates to a support with a drug for administering a drug to the eye.

  Conventionally, eye drops are widely known as ophthalmic preparations. In the case of eye drops, since a liquid medicine stored in an eye drop container is dropped and administered, the drop amount differs depending on the pressing force of the eye drop container, and the intended drop amount may not be administered.

  On the other hand, a method of inserting a solid composition for ophthalmology into the eye is known as means for administering a fixed amount of a drug to the eye. Since this kind of solid composition contains a pharmaceutical component necessary for one administration in one solid composition, it can be administered in a certain amount, but the solid composition can be administered directly by hand. Therefore, it was difficult to maintain a sterilized state.

  As an ophthalmic agent intended to solve the above-described problems, Patent Document 1 discloses an applicator for administering a drug to a wet biological surface. That is, in this applicator, a matrix layer containing a drug component in a soluble matrix is provided at one end of a disposable applicator having a long and narrow band shape. A separation portion whose thickness is thinner than other portions is formed in the middle of the matrix layer (see FIG. 1 of Patent Document 1). In this applicator, by holding the other end of the applicator opposite to the drug body and bringing the drug body into contact with the living body surface that is the administration site, the thinner separation part dissolves and the drug body. Is separated from the applicator and the drug main body is administered, so that a certain amount of drug can be administered while maintaining the sterilized state when the drug is administered.

Japanese Examined Patent Publication No. 4-11229

  However, it was very difficult to form a separation part thinner than other parts in a matrix layer that was originally not so thick. Even if the separation part can be formed, the difference between the solubility of the separation part and the solubility of other parts is not sufficient, for example, the separation part is separated at the tip side from the separation part in the matrix layer. Could not be administered.

  This invention is made | formed in view of the background mentioned above, and it is providing the support body with a chemical | medical agent which can administer a fixed quantity of chemical | medical agents reliably to eyes.

A support with a drug for administering a drug to the eye according to the present invention,
A drug layer comprising a drug and a water-soluble polymer;
A dissolution separation layer comprising a water-soluble polymer set to have a higher water solubility than the water-soluble polymer of the drug layer;
With a support to be a handle,
The drug layer and the support are connected to the opposite side via the dissolution separation layer.

According to this configuration, the form of the drug layer and the dissolution / separation layer is not particularly limited. However, for example, a film-like form is preferable, and the support is a handle of the support with the drug, and the application at the time of drug administration is performed. Can be used as data. Therefore, the drug-supported support of the present invention can administer the drug while maintaining a sterilized state.
Further, the solubility of the dissolution / separation layer provided between the drug layer and the support is higher than the water solubility of the drug layer. For this reason, when the drug is administered, the dissolution / separation layer dissolves before the drug layer on the surface of the eye, so that the drug layer is separated from the support with the drug and administered to the surface of the eye. As a result, a certain amount of drug (drug layer) can be reliably administered.
As described above, it is possible to provide a drug-supported support capable of reliably administering a certain amount of drug.

  In the above configuration, it is preferable that all or a part of the drug layer and a part of the dissolution / separation layer overlap each other.

  By increasing the overlap (contact area) between 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 preferable that the dissolution separation layer and the support are partially overlapped.
By connecting the drug layer, the dissolution / separation layer, and the dissolution / separation layer and the support in an overlapping manner, the connection strength can be increased with the drug layer, the dissolution / separation layer, and the support as one body.

  In the above configuration, it is preferable that the drug layer, the dissolution / separation layer, and the dissolution / separation layer and the support are securely connected by thermocompression bonding or adhesion.

  In the above-described configuration, the average disintegration time of the dissolution separation layer (disintegration time is the time required for the film-like matrix of a certain size to dissolve in water or physiological saline) is 60 seconds or less, more preferably 50 seconds or less. is there. This is because if the average disintegration time of the dissolved separation layer exceeds 60 seconds, it takes too much time to administer the drug to the eye using the drug-supported support.

  With this configuration, since the dissolution / separation layer dissolves quickly on the ocular surface, a certain amount of drug can be quickly administered to the ocular surface.

It is a side view which shows an example of the support body with a medicine concerning the present invention. It is a top view which shows an example of the support body with a medicine concerning the present invention. It is a figure which shows the use condition of a support body with a chemical | medical agent. It is a side view which shows the support body with a medicine concerning another embodiment of the present invention. It is a side view which shows the support body with a medicine concerning another embodiment of the present invention. It is a side view which shows the support body with a medicine concerning another embodiment of the present invention. It is a side view which shows the support body with a medicine concerning another embodiment of the present invention. It is a side view which shows the support body with a medicine concerning another embodiment of the present invention. It is a side view which shows the support body with a medicine concerning another embodiment of the present invention.

  Below, embodiment of the support body 1 with a chemical | medical agent which concerns on this invention is described based on drawing. However, the present invention is not limited to the following embodiments, and various modifications can be made without departing from the scope of the invention.

  As shown in FIG. 1, the drug-supported support 1 is composed of a film-like drug layer 2, a film-like dissolution / separation layer 4, and a support 3 serving as a handle, and the size of the drug layer 2 is not particularly limited. However, for example, the width is preferably about 1 to 4 mm, the length is about 5 to 10 mm, and the thickness is 1 to 300 μm. The size of the dissolution separation layer 4 is not particularly limited, but for example, the width is about 1 to 4 mm and the length 3 to 3 It is preferably about 10 mm and a thickness of 1 to 300 μm, and the size of the support 3 is not particularly limited. For example, the width is about 1 to 4 mm, the length is about 10 to 60 mm, and the thickness is 50 μm to 2 mm. Is preferred.

  The support 3 has, for example, a long and thin rectangular shape and serves as a handle for maintaining a sterilized state. Although the material of the support body 3 is not specifically limited, Paper, plastics, aluminum foil, etc. are applicable suitably. Further, the support 3 may be formed by laminating a plurality of these layers.

As shown in FIGS. 1 and 2, the drug layer 2 and the support 3 are connected to the opposite side via the dissolution / separation layer 4, and the dissolution / separation layer 4 is provided between the drug layer 2 and the support 3. . More specifically, each of the drug layer 2 and the dissolution / separation layer 4 is a film-like matrix, and is connected by adhering the entire lower surface of the drug layer 2 and a part of the upper surface of the dissolution / separation layer 4. Then, a part of the lower surface of the dissolution separation layer 4 and a part of the upper surface of the support 3 are connected by thermocompression bonding or adhesion. Thus, the connection strength can be increased by connecting the drug layer 2 and the dissolution / separation layer 4 and the dissolution / separation layer 4 and the support 3 in an overlapping manner and increasing the respective contact areas.
In addition, the connection method between the drug layer 2 and the dissolution / separation layer 4 and the connection method between the dissolution / separation layer 4 and the support 3 may be connected by methods other than thermocompression bonding and adhesion.

The drug layer 2 is composed of a matrix containing a water-soluble polymer and a drug, and an emulsifier such as polysorbate 80 and a plasticizer such as glycerin can be blended in the matrix as necessary. These water-soluble polymers can be mixed, or a matrix having two or more kinds of multilayer structures can be formed.
The dissolution / separation layer 4 is composed of a matrix containing a water-soluble polymer that does not contain a drug, and an emulsifier and a plasticizer can be blended in the matrix as necessary, and mannitol is used to enhance water solubility. It is also possible to add a water-soluble polymer having a low molecular weight, such as sugar alcohol, oligomers, and telomers, or to introduce bubbles. If necessary, two or more water-soluble polymers can be mixed. The matrix constituting the dissolution / separation layer 4 is set to have higher water solubility than the matrix constituting the drug layer 2. In this way, by making the water solubility of the dissolution / separation layer 4 higher than that of the drug layer 2, the dissolution / separation layer 4 dissolves before the drug layer 2 if it comes into contact with tears during administration. Further, by providing the dissolution / separation layer 4 having a higher water solubility than the drug layer 2, there is no problem such as separation from the middle part of the drug layer 2 during administration, and the drug layer 2 is separated from the support 1 with the drug. Since it adheres to the ocular surface, a certain amount of drug can be reliably administered (see FIGS. 1 to 3).

  As an indicator of water solubility, the average disintegration time for water or physiological saline when a film-like matrix having a certain size [2 × 7 mm, film thickness of about 30 μm], which will be described in detail in the examples, can be applied. . For example, the average disintegration time of the matrix constituting the drug layer 2 is not particularly limited, but is preferably 100 minutes or less.

  Further, the average disintegration time of the film-like matrix constituting the dissolution / separation layer 4 is not particularly limited because the dissolution / separation layer 4 is more easily dissolved by tears on the ocular surface as the solubility in water or physiological saline increases. 60 seconds or less, more preferably 50 seconds or less. This is because if the average disintegration time of the dissolved separation layer 4 exceeds 60 seconds, it takes too much time to administer the drug to the eye using the drug-supported support 1. That is, by setting the average disintegration time of the dissolution / separation layer 4 to 60 seconds or less, the dissolution / separation layer 4 quickly dissolves in the tears on the ocular surface, and a certain amount of drug can be quickly administered to the ocular surface. .

  The average disintegration time of the film-like matrix constituting the drug layer 2 is larger than the average disintegration time of the film-like matrix constituting the dissolution / separation layer 4, and the difference is not particularly limited but is preferably 1 second or more. Is 2 seconds or more. That is, by setting the difference in average disintegration time as described above, the dissolution / separation layer 4 dissolves before the drug layer 2 on the surface of the eye at the time of administration, and the drug layer 2 is separated from the drug-supported support 1 to the eye. Can be administered on the surface of When the drug layer 2 and a part of the dissolution / separation layer 4 are laminated and connected, the sum of the average disintegration time of the drug layer 2 and the average disintegration time of the dissolution / separation layer 4 is the average of the dissolution / separation layer 4. By setting so as to be longer than the disintegration time, more preferably 2 seconds or more, the dissolution / separation layer 4 can be dissolved on the surface of the eye before the laminate of the drug layer 2 and the dissolution / separation layer 4. .

  Based on the above, the matrix constituting the drug layer 2 is not particularly limited as long as it is a water-soluble matrix. For example, cellulose-based water-soluble polymer, acrylate polymer, polyvinyl pyrrolidone, polyvinyl alcohol, poly (ethylene oxide), polysaccharides Specifically, CMC Daicel 1205 (average disintegration time 10 seconds, manufactured by Daicel Finechem), PLASDONE K-90 (average disintegration time 11 seconds, manufactured by Ashland), HPC-L (average disintegration time 27 seconds) Manufactured by Nippon Soda Co., Ltd.), Gohsenol EG-05 (average disintegration time 29 seconds, manufactured by Nippon Synthetic Chemical Co., Ltd.), TC-5S (average disintegration time 34 seconds, manufactured by Shin-Etsu Chemical Co., Ltd.), Metrose 60SH-50 (average disintegration time 43 Second, manufactured by Shin-Etsu Chemical Co., Ltd.), Metroz SM15 (average decay time 138 seconds, Shin-Etsu Chemical) Manufactured), Metrows SM100 (average decay time 162 seconds, manufactured by Shin-Etsu Chemical Co., Ltd.), Celny M (average collapse time 287 seconds, manufactured by Nippon Soda Co., Ltd.), Kimika Argin IL-2 (average decay time 332 seconds, manufactured by Kimika), HEC Those containing a water-soluble polymer such as Daicel SE400 (average disintegration time of 1800 seconds or more, manufactured by Daicel FineChem) are preferably used.

  Examples of the matrix constituting the dissolution / separation layer 4 include cellulose-based water-soluble polymers, polyvinyl pyrrolidone, polyvinyl alcohol, and the like. Specifically, CMC Daicel 1205 (average disintegration time 10 seconds, manufactured by Daicel Finechem), PLASDONE K-90 (average disintegration time 11 seconds, manufactured by Ashland), HPC-L (average disintegration time 27 seconds, manufactured by Nippon Soda Co., Ltd.), Gohsenol EG-05 (average disintegration time 29 seconds, manufactured by Nippon Synthetic Chemical Co., Ltd.), Those containing a highly water-soluble polymer such as TC-5S (average disintegration time 34 seconds, manufactured by Shin-Etsu Chemical Co., Ltd.), Metrose 60SH-50 (average disintegration time 43 seconds, manufactured by Shin-Etsu Chemical Co., Ltd.) are preferably used.

  The combination of the matrix constituting the drug layer 2 and the matrix constituting the dissolution / separation layer 4 is not particularly limited. Examples of the matrix constituting the drug layer 2 include water-soluble polymers such as HPC-L and Metrose SM15. Moreover, as a matrix which comprises the melt | dissolution separation layer 4, it is suitable to contain water-soluble polymers with higher water solubility, such as PLASDONE K-90 and CMC Daicel 1205, for example.

  Next, the usage method of this support body 1 with a chemical | medical agent is demonstrated. The case where the drug layer 2 is administered to the ocular surface will be described as an example. For example, it is administered to the anterior segment of the cornea, eyelid conjunctiva or conjunctival fistula. As shown in FIG. 3, the user picks the vicinity of the end of the support 3 opposite to the end on the side where the drug layer 2 of the support 1 with the drug is provided, and administers the drug layer 2. Move closer to the site. In the present embodiment, the lower eyelid is pulled down with the finger of one hand to expose the conjunctiva, and the region near the end opposite to the side on which the drug layer 2 is provided of the support 3 with the finger of the other hand The drug layer 2 and the dissolution / separation layer 4 are brought close to the eye surface and brought into contact with the exposed conjunctiva. At this time, the water solubility of the dissolution / separation layer 4 is higher than the water solubility of the drug layer 2, so that the drug separation layer 4 is quickly separated from the support 3 as a result of the dissolution / separation layer 4 being dissolved in tears. Adhere to. Thus, in this support body 1 with a medicine, it does not separate in the middle part of the medicine layer 2, and a certain amount of medicine (the medicine layer 2) can be reliably administered.

[Another embodiment]
Another embodiment of the drug-supported support 1 according to the present invention is shown in FIGS. In FIG. 4, a part of the lower surface of the drug layer 2 and a part of the upper surface of the dissolution / separation layer 4 are connected, and a part of the lower surface of the dissolution / separation layer 4 and a part of the upper surface of the support 3 are connected. Has been. In FIG. 5, the entire lower surface of the drug layer 2 and a part of the upper surface of the dissolution / separation layer 4 are connected, and the upper surface of the dissolution / separation layer 4 and a part of the lower surface of the support 3 are connected. ing. In FIG. 6, a part of the lower surface of the drug layer 2 and a part of the upper surface of the dissolution / separation layer 4 are connected, and a part of the upper surface of the dissolution / separation layer 4 and a part of the lower surface of the support 3 are connected. Has been. In FIG. 7, the entire lower surface of the drug layer 2 and a part of the upper surface of the dissolution / separation layer 4 are connected, and the upper and lower surfaces of the dissolution / separation layer 4 and the upper and lower surfaces of the support 3 are connected without overlapping. Yes. In FIG. 8, the drug layer 2, the dissolution separation layer 4, and the upper and lower surfaces of the support 3 are all connected without overlapping. FIG. 9 shows a form in which the entire lower surface of the drug layer 2 and a part of the upper surface of the dissolution / separation layer 4 are connected, and the two supports 3 sandwich the dissolution / separation layer 4. In FIG. 9, the support 3 and the dissolution / separation layer 4 do not necessarily require thermocompression bonding or bonding.

[Experimental example]
(1) Measurement method and measurement result of average disintegration time of film matrix CMC Daicel 1205 [Polymer A] 18.0% (w / w) as water-soluble polymer, glycerin 1.62% (w / w) as plasticizer Sample 1 was prepared by dissolving a water-soluble polymer (CMC Daicel 1205), a plasticizer (glycerin) and an emulsifier (polysorbate 80) in a solvent (water) so that the polysorbate 80 was 0.09% (w / w) as an emulsifier. Was made. Further, PLASDONE K-90 [Polymer B], HPC-L [Polymer C], Gohsenol EG-05 [Polymer D], TC-5S [Polymer E], Metrolose 60SH-50 are performed by performing the same operation. [Polymer F], Metrolz SM15 [Polymer G], Metrolz SM100 [Polymer H], Celny M [Polymer I], Kimika Argin IL-2 [Polymer J] and HEC Daicel SE400 [Polymer K] are used as solvents (water, ethanol, water Samples 2 to 11 were prepared as shown in Table 1 by adding glycerin as a plasticizer and polysorbate 80 as an emulsifier as necessary. Next, samples 1 to 11 were applied on a polypropylene film base material using an applicator so as to have a thickness of about 30 μm, and dried with warm air. Next, each of the obtained film-like matrices is chopped into 2 × 7 mm sizes, immersed in 10 mL of physiological saline at room temperature, and the disintegration time of the film-like matrix [until the matrix completely dissolves and disappears. Time]. The results are shown in Table 1. In addition, the average disintegration time of each film-form matrix obtained from the samples 1-11 is an average value of disintegration time when measured 3 times.

(2) Preparation of a drug-supported substrate Fluorescein sodium is added to each sample [Samples 1, 3, 6, 7, 10, 11] so that it becomes 10% (w / w) of sodium fluorescein as a substitute drug. A layer coating solution was prepared. This drug layer coating solution was applied onto a polypropylene film base material using an applicator so as to have a thickness of about 30 μm and a width of 7 mm, and dried with warm air. Next, on the drug layer applied to the base material, the coating solution for dissolving / separating layer (samples 1, 2, 6, 10, 11) is made to have a thickness of about 30 μm and a width of about 50 mm using an applicator. Then, a dissolved separation layer was formed on the drug layer and dried with warm air to obtain each laminated film. After separating each laminated film from the base material and connecting the laminated film and a support (separate paper) with an adhesive, the obtained support with a drug was chopped to a size of 2 × 50 mm. Table 2 shows the types of water-soluble polymers constituting the drug layers and the dissolution / separation layers of Examples 1 to 4 and Comparative Examples 1 and 2 and their average disintegration time.

実施例１〜４の薬剤付き支持体は、１０秒以内に薬剤層が支持体から分離され、その全量をウサギ結膜部に投与できた。
したがって、本発明の薬剤付き支持体を用いれば、眼に一定量の薬剤を確実に投与できる。 (3) Ophthalmic administration test using rabbits At the center of the right lower eyelid conjunctiva of normal rabbits (acupuncture, Japanese white species, Kitayama Labes), the dissolution / separation layer side of each drug-supported support prepared in (2) above After pressing for 10 seconds, it was collected and it was visually determined whether or not the entire amount of the drug layer could be administered to the rabbit conjunctiva. When the total amount of the drug layer can be administered to the rabbit conjunctiva is “1”, and when the drug layer cannot be administered at all or only part of the drug layer is “0”, this operation is repeated three times The total score was calculated. Table 2 shows the results. In addition, Examples 1-2 are the support bodies with a chemical | medical agent of the form of FIG. 1 with which all the lower surfaces of the chemical | medical agent layer 2 and some upper surfaces of the melt | dissolution separation layer 4 were connected, and Examples 3-4 And Comparative Examples 1-2 are the support bodies with a chemical | medical agent of the form of FIG. 4 with which a part of lower surface of the chemical | medical agent layer 2 and a part of upper surface of the melt | dissolution separation layer 4 were connected.

As for the support body with a chemical | medical agent of Examples 1-4, the chemical | medical agent layer was isolate | separated from the support body within 10 second, and the whole quantity was able to be administered to a rabbit conjunctiva part.
Therefore, when the drug-supported support of the present invention is used, a certain amount of drug can be reliably administered to the eye.

  The present invention can be applied to a drug-supported substrate for drug administration to the eye.

DESCRIPTION OF SYMBOLS 1 Support body with medicine 2 Drug layer 3 Support body 4 Dissolution separation layer

Claims (5)

A drug layer comprising a drug and a water-soluble polymer;
A dissolution separation layer comprising a water-soluble polymer set to have a higher water solubility than the water-soluble polymer of the drug layer;
With a support to be a handle,
A support with a drug for administering a drug to the eye, wherein the drug layer and the support are connected to the opposite side via the dissolution separation layer.   The support with a drug according to claim 1, wherein all or a part of the drug layer and a part of the dissolution / separation layer overlap each other.   The support body with a chemical | medical agent of Claim 2 with which a part of said melt | dissolution separation layer and a part of said support body have overlapped.   The support body with a medicine according to any one of claims 1 to 3, wherein the dissolution separation layer and the support body are thermocompression-bonded or bonded. The support with a medicine according to any one of claims 1 to 4, wherein an average disintegration time of the dissolution / separation layer with respect to water or physiological saline is 60 seconds or less.

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