JPH08291055A - Shape memory plaster - Google Patents

Abstract

PURPOSE: To obtain a plaster having a shape memory function, excellent in skin adhesivity, scarcely generating poorly adhesive spaces when plastering, exhibiting excellent motion stretchability during use and durable for the several repetitions of adhesion and peeling cycles. CONSTITUTION: This shape memory plaster is composed of (A) a shape memory plastering body 1, (B) a shape memory supporting body or the combination of the both components. Further, the supporting body having stretchability and air permeability preferably consists of a shape memory alloy fiber cloth or a laminated body of a protein fiber attached with a phosphoramide compound or a copolyester fiber on a fusing binder fiber, and it has a shape memory function at the body temperature. The plastering body 1 is preferably composed of a dissolution agent (e.g. castor oil) for the principal ingredients, a polyacrylic acid or its salt as a form and moisture retaining agent, hydroxylated alumina magnesium, sorbitol, and an absorption-stimulating and flavoring agent (e.g. camphor or menthol).

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a ketoprofen patch, and more particularly to a patch made of a shape memory material and a method for administering a patch for systemic effects and conventional local effects.

[0002]

2. Description of the Related Art Ketoprofen has been researched and developed by the present inventors in Japan as an oral or injectable drug for the purpose of antipyretic analgesia (Japanese Pharmacopoeia 70, 543 pages, 1974), and as a local analgesic (muscle pain, etc.), ointment. Agents and poultices have been used for a long time (1979 INFORMATORE FARMACEUTICO 4
66 pages, Japanese Patent Publication No. 2-28572, Japanese Patent Publication No. 6-62401, etc.). In addition, recently, studies have been conducted on various drugs for patch bases that have good absorbability and are easy to control and control disease status, age, sex, weight, skin epidermal area, and patching time (Patent Publication 4- No. 50291).

Since a transdermal drug administration method for the purpose of systemic effect is expected to have various advantages such as suppression of liver degradation and occurrence of side effects, it has recently been highlighted.
Various formulations have been put on the market by the applicant company, etc. (Investigator Information, page 238, Medical Affairs Publisher, 1992).

Shape memory materials have recently been applied to clothes such as those using metal or plastic fiber, and those to which phosphorus amide material is attached, but catheters are applicable to pharmaceutical products. However, there is almost no research on patches and ointment bases themselves. (JP-A-5-44128,5-51853,5-7893
No. 2 etc.)

[0005]

[Problems and problems to be solved by the invention] The patch is likely to lose its shape due to body temperature, moisture absorption, etc. several hours after the patch is applied, and if the patch is poor, the plaster may flow out or bubbles may be generated on the skin surface. It has been pointed out that it is easy to peel it off.

[0006] The method of administration by percutaneous absorption, the patch, and the method of percutaneous absorption by patches and tapes are used for those who cannot be administered orally or by injection, such as infants and the elderly, and the suppression of liver degradation and the occurrence of side effects. It has various advantages such as suppression and is a very ideal dosing method. However, there is a problem of shape loss as described above, and it is difficult to control absorption and dosing, so it is recommended to use a small amount of a well-absorbed active agent such as isosorbide, nitroglycerin, or clonidine as a patch or tape. It was limited.

[0007] Ketoprofen has fewer side effects than similar drugs such as indomethacin, and injections, oral preparations, capsules, and suppository forms are used as antipyretic analgesics. However, it is difficult to control the adhesiveness, release property, and the like of the form of a poultice or tape, and therefore, it is used only for the purpose of local analgesic and anti-inflammatory.

[0008] In addition, oral use of ketoprofen requires caution in administration to infants and people who have experienced peptic ulcer, and discomfort, stomach pain, loss of appetite, vomiting, nausea, diarrhea, etc. have been reported as side effects, and management It was desired to develop a patch that is easy to control.

The present inventors have already developed an ideal ointment base suitable for transdermal administration. As a result of trying to solve the above-mentioned problems of ketoprofen by using this ointment base , Stretchable and breathable support, ketoprofen {2- (m-benzoylphenyl) propionic acid} 0.3-3 wt% relative to the amount of plaster, and castor oil as a solubilizer
0.5 to 2% by weight, and 2 to 10% by weight of polyacrylic acid or its salt as a shape-retaining / humidifying agent, 0.2 to 3% by weight of magnesium alumina hydroxide and 20 to 50% by weight of sorbitol to promote absorption. And, it was discovered that a formulation containing 0.5 to 2% by weight of camphor or menthol as an fragrance has improved shape memory properties, is rich in skin adhesiveness and elasticity, and is relatively easy to control absorption, The present invention has been completed.

In addition to the effects of the conventional ketoprofen patch for the purpose of local antiphlogistic and analgesia, the present invention proposes the possibility of using it as an antipyretic analgesic even for patients who dislike oral administration such as infants. It also provides an ideal ketoprofen transdermal drug delivery alternative to oral administration.

Even for the purpose of local antiphlogistic and analgesia, a soft base having excellent drug release and a good shape memory property can be used to obtain a formulation in which the dose of ketoprofen can be accurately controlled, and further tablets. It is intended to provide a preparation that can be safely used by infants, debilitated people, and elderly people by devising a cutting line instead of the discount.

Since the present invention has a shape memory property, in addition to the above-mentioned dosage control, elasticity during exercise, pressurization,
Can withstand changes in hardness of plasters at body temperature. For this reason, the shape does not collapse even when used for a long time, the adhesiveness is excellent, and the occurrence of air pockets can be suppressed even when repeated proper desorption and adhesion during exercise, and the dosage can be accurately controlled.

As a patch comprising a shape memory plaster and a shape memory support or a combination thereof, the method of the present invention can be used for most of transdermal medicines. For example, in addition to ketoprofen of the examples of the present invention, indomethacin, antipyretic anti-inflammatory analgesics such as flurbiprofen, steroids, peptide hormones, nitroglycerin,
It can be applied to circulatory agents such as clonidine and isosorbide dinitrate, and anti-asthma agents such as formotere fumarate, dimorphan phosphate, carbetapentane citrate, and procaterol hydrochloride. In addition, it can be applied to a drug that could not be used as a transdermal drug because it is impossible to control the skin adhesiveness.

[0014]

The present invention relates to a support having stretchable and breathable property, preferably shape memory property.
Ketoprofen {2- (m-benzoylphenyl) propionic acid} 0.3-3% by weight, castor oil 0.5-2% by weight as a solubilizer, and a shape-retaining / humectant, relative to the amount of plaster.
Containing 2 to 10% by weight of polyacrylic acid or its salt, 0.2 to 3% by weight of alumina magnesium hydroxide, 20 to 50% by weight of sorbitol, and containing 0.5 to 2% by weight of camphor or menthol as an absorption accelerating and aromatic agent. Based on a ketoprofen poultice, which is characterized by the fact that the support is a woven or non-woven fabric using shape memory alloy fibers, in addition to the systemic action as an antipyretic analgesic, the dosage is For accurate preparation, a liner (release paper) or a plaster having a shape in which a cutting line that can be cut with scissors is printed on the back surface of the plaster is included.

In actual use, in the case of aiming at systemic action, the disease status, age, sex, weight of the target patient,
An accurate pharmacological effect can be expected by calculating the application time from the skin epidermal area and controlling the medication.

For the purpose of local action, a method of cutting the patch from the patient's condition, age, sex, body weight, and skin epidermis area can be used.

The ketoprofen patch according to the present invention uses a castor oil, menthol and camphor as a dissolution agent and an absorption enhancer to diffuse and disperse ketoprofen in a shape-memory base in a semi-dissolved state. For the purpose of retaining the above properties and further maintaining good adhesiveness during exercise, a material in which gelatin, glycol, polyacrylic acid, sorbitol, sorbitan, etc. are combined is selected as a shape memory base.

As the shape memory plaster support used in the present invention, a protein fiber thread to which a phosphorus amide compound is attached, a copolyester fiber / heat-fusible binder fiber laminate, Ni
It is possible to use a relatively easy-to-process fiber material having a shape memory function at body temperature, such as a shape memory alloy fiber thread such as / Ti. Hereinafter, the present invention will be described in more detail with reference to examples.

[0019]

【Example】

Formulation Example 1 (Shape memory base patch) A patch having the following formulation was prepared per patch (paste 10 g, 10 × 14 cm).

Formulation Example 2 (Shape patch using shape memory base) A patch having the following formulation was prepared per patch (paste 10 g, 10 × 14 cm).

Formulation Example 3 A formulation was prepared by applying the plaster of Production Example 1 using a copolyester type shape memory woven fabric (made by Unitika) as a support.

Formulation Example 4 A formulation was prepared in which the plaster described in Production Example 2 was applied using a phosphoramide type shape memory woven fabric (manufactured by Nitto Boseki) as a support.

Formulation Example 5 (Comparative Example 1)

Formulation Example 6 (Comparative Example 2) Paste Ketoprofen 0.30 Alumina magnesium hydroxide 0.01 Kaolin 0.05 Sorbitol 3.00 Gelatin 0.06 Polyvinyl alcohol 0.04 Glycerin 2.50 Mint oil 0.01 Hydroxymethoxybenzophenone 0.01 Dihydroxytoluene 0.03 Purified water Appropriate amount Total 10.0g Support Non-woven fabric Liner Polypropylene

Test Example 1 (Shape Memory Test and Formulation Material Test) Test Method Shape Memory Test 1) Improvement test of central deformed state Maintain room temperature at 35 ° C and fix 1cm square around 10cm × 14cm formulation Then, 20 g of weight was placed on the central part, and the weight was removed after 6 hours, and the improvement of the deformed state of the central part was examined.

2) Tensile test 1 cm of the peripheral part of the formulation 10 cm × 14 cm is fixed and 3 in one direction
After the stretching of cm, the recovery property after removal was examined 6 hours later.

3) Compression test 10 cm × 14 cm of the preparation is placed on an iron plate, and 2 kg is placed on the upper surface.
6 hours after the iron plate was placed, the exuding state of the plaster from the four sides of the preparation due to pressurization was examined.

Cutout Test A volunteer was asked to cut the central part of the preparation together with release paper with the same scissors, and a questionnaire survey was conducted on the number of cuts per minute and the adhesiveness of the plaster to the blade part of the scissors.

The results are shown in Table 1 below.
It was found that the preparation of No. 4 was excellent in shape memory, had less adhesiveness of the plaster to the blade portion of the scissors, and was easy to cut.

[0030]

[Table 1] Formulations 1 to 2 of the present invention 3 to 4 Comparative formulations (5 to 6) Shape memory 1) Deformation in central part Some deformation No deformation Deformation (non-recoverable) 2) Tensile deformation No deformation No deformation (non-recoverable) 3) Compression test No plaster elution No plaster elution Occurrence of plaster elution Cut out Number of cuts per minute 25 or more 16 or more About 4 4 sheets It turns out that it is necessary)

Test Example 2 (Transdermal Absorption Test) The antipyretic and analgesic effect of the preparation of the present invention was tested. The back of the rat is dehaired to make 5 mice per group, 20% brewer's yeast 10 mg
/ kg was subcutaneously administered, and 16 hours later, the preparation of the present invention was 2.16 cm square.
Cut to (4.7 cm ² ) (containing 10 mg as ketoprofen)
It was adhered and fixed to the hair-removed part to make a transdermal administration group. Furthermore, 5 mg / kg of ketoprofen (keto) was orally administered as an oral administration group, and the rectal temperature was measured every 6 hours using a thermistor thermometer.
Measured 6 times up to the time, and summed up the time difference of the temperature difference of each administration group between the dermal administration group and the oral administration group (total of 6 times)
Was taken as the antipyretic coefficient. As a result, as shown in Table 2 below, it was found that Formulation Example 4 of the present invention was the most excellent.

[0032]

[Table 2]

Test Example 3 (Evaluation of feeling of use) The formulation of the present invention was asked by 20 panelists with myalgia to cooperate with each of the five formulations of Formulation Examples 3 and 4 as well as Morus (Hisami Pharmaceutical Co., Ltd.) and the formulation as controls. Example 6 was used in a timely manner and the feeling of use was evaluated. Evaluation of feeling of use: A questionnaire survey was conducted on the anti-inflammatory and analgesic effect, adhesiveness, adhesiveness, elasticity, and skin condition (itch, redness, etc.). The results are shown in Table 3 below, and the formulations of the present invention were well received.

[0034]

[Table 3] Inventive product Control product Formulation example 3 Formulation example 4 Morus Formulation example 6 a) Anti-inflammatory and analgesic effect is good 5 5 5 0 b) Adhesiveness at the time of application is good 5 5 3 0 c) Air bubbles are generated during application 0 0 3 5 d) Occurrence of itch during application 0 0 2 2 e) Good stretchability during exercise 5 5 20 f) Peeling after exercise occurs 0 0 2 5 g) Adhesiveness Can be attached several times even if peeled off 5 5 10 h) State of pasted part after peeling Occurrence of itch 0 0 1 2 Redness 0 1 1 3 Adhesion of adhesive 0 0 1 5 i) Feel of use (discovery for several days after peeling) Change of skin Hot 0 0 25 Redness 0 0 0 2 Itching occurred 0 0 0 2

[0035]

EFFECTS OF THE INVENTION High skin adhesiveness, little occurrence of defective adhesion space at the time of application, and excellent motion elasticity during use,
It can withstand several adhesion-peeling environments. It is also a non-irritating and non-irritating preparation that is easy to use. It is possible to control the dosage by breaking or adding a breaking line, and it can be applied as a drug for infants, debilitated people, and elderly people.

[Brief description of drawings]

FIG. 1 is an external view of an example of the shape memory preparation according to the present invention.

[Explanation of symbols]

1-Release paper with disconnection printed or engraved for dosage adjustment 2 Shape memory non-woven fabric to which paste with engraved disconnection for dosage adjustment 3 attached-Shape memory plaster containing ketoprofen

─────────────────────────────────────────────────── ───

[Procedure amendment]

[Submission date] April 20, 1995

[Procedure Amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0011

[Correction method] Change

[Correction content]

Further, even for the purpose of local anti-inflammatory and analgesia, a formulation capable of accurately controlling the dosage of ketoprofen by using an ointment base which is excellent in drug release and has a good shape memory property, and further tablets It is intended to provide a preparation that can be safely used by infants, debilitated people, and elderly people by devising a cutting line instead of the discount.

[Procedure Amendment 2]

[Document name to be amended] Statement

[Correction target item name] 0013

[Correction method] Change

[Correction content]

As a patch comprising a shape memory plaster and a shape memory support or a combination thereof, the method of the present invention can be used for most of transdermal medicines. For example, in addition to ketoprofen of the present invention examples, indomethacin, antipyretic anti-inflammatory analgesics such as flurbiprofen, steroids, peptide hormones, nitroglycerin,
It can be applied to circulatory agents such as clonidine and isosorbide dinitrate, and anti-asthma agents such as formotere fumarate, dimorphan phosphate, carbetapentane citrate, and procaterol hydrochloride. In addition, it can be applied to a drug that could not be used as a transdermal drug because it is impossible to control the skin adhesiveness.

[Procedure 3]

[Document name to be amended] Statement

[Correction target item name] 0018

[Correction method] Change

[Correction content]

As the shape memory plaster support used in the present invention, a protein fiber thread to which a phosphorus amide compound is attached, a copolyester fiber / heat-fusible binder fiber laminate, Ni
It is possible to use a fiber material that is relatively easy to process so as to have a shape memory function at body temperature, such as a shape memory alloy fiber thread such as / Ti. Hereinafter, the present invention will be described in more detail with reference to examples.

[Procedure amendment 4]

[Document name to be amended] Statement

[Correction target item name] 0028

[Correction method] Change

[Correction content]

Cut-off test A volunteer was asked to cut the central part of the preparation together with release paper with the same scissors, and a questionnaire survey was conducted on the number of cuts per minute and the adhesiveness of the plaster to the blade part of the scissors.

[Procedure Amendment 5]

[Document name to be amended] Statement

[Correction target item name] 0035

[Correction method] Change

[Correction content]

[0035]

EFFECTS OF THE INVENTION High skin adhesiveness, little occurrence of defective adhesion space at the time of application, and excellent motion elasticity during use,
It can withstand several adhesion-peeling environments. It is also a non-irritating and non-irritating preparation that is easy to use. Since the dosage can be controlled relatively accurately, it can be applied as a drug for infants, debilitated people, and elderly people.

[Procedure correction 6]

[Document name to be amended] Statement

[Name of item to be corrected] Brief description of the drawing

[Correction method] Change

[Correction content]

[Brief description of drawings]

FIG. 1 is an external view of an example of the shape memory preparation according to the present invention.

FIG. 2 is an external view of an example in which the shape memory fiber cloth according to the present invention is used as a support.

[Explanation of Codes] 1-Release paper printed or engraved with disconnection lines for dose adjustment 2 Ketoprofen-containing shape memory plaster 3 -Shape to which paste with engraved disconnection lines for dose adjustment is attached Memory nonwoven fabric 4 ~ Release paper 5 ~ Paste 6 ~ Shape memory fiber cloth 7 ~ Nonwoven fabric

[Procedure Amendment 7]

[Document name to be corrected] Drawing

[Name of item to be corrected] Figure 1

[Correction method] Change

[Correction content]

FIG.

[Procedure Amendment 8]

[Document name to be corrected] Drawing

[Name of item to be corrected] Figure 2

[Correction method] Added

[Correction content]

[Fig. 2]

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Reference number within the agency FI Technical display area A61K 31/19 ABE A61K 31/19 ABE 47/02 47/02 F 47/10 47/10 F D04H 1/54 D04H 1/54 H D06M 13/44 D06M 13/44

Claims (5)

[Claims] 1. A patch having a shape memory function, which comprises a shape memory plaster and a shape memory support or a combination thereof. 2. A stretchable and breathable support comprising a shape memory alloy fiber cloth, a protein fiber thread to which a phosphorus amide compound is attached, or a copolyester fiber / heat-fusible binder fiber laminate, and the shape at body temperature. A patch characterized by having a memory function. 3. A plaster comprises a dissolving agent for the main drug, polyacrylic acid or a salt thereof as a shape-retaining / moisturizing agent, magnesium alumina hydroxide, sorbitol and an absorption-promoting and fragrance agent, which has a shape-memory function at body temperature. A patch characterized by having. 4. A support having stretchable and breathable properties, wherein ketoprofen {2- (m-benzoylphenyl) is used with respect to the amount of paste.
0.3 to 3% by weight of propionic acid, 0.5 to 2% by weight of castor oil as a solubilizer, 2 to 10% by weight of polyacrylic acid or a salt thereof as a shape-retaining / moisturizing agent, and 0.2 to 3 of magnesium alumina hydroxide. A shape memory ketoprofen patch characterized by containing 20% to 50% by weight of sorbitol and 0.5% to 2% by weight of camphor or menthol as an absorption accelerating and aromatic agent. 5. The patch is used by cutting from the subject's disease, age, sex, weight and skin-epidermal area before use.
The ketoprofen patch according to claim 1, wherein the ketoprofen patch is provided with a disconnection line or a cutout line printed on the liner portion.