JPS635032A - Stabilized plaster containing melanoidin - Google Patents

Abstract

PURPOSE:To provide the titled plaster by adding melanoidin to a plaster composed of a pressure-sensitive adhesive substance. CONSTITUTION:A stabilized plaster can be produced by compounding a plaster composed of a pressure-sensitive adhesive substance with melanoidin (having a molecular weight of 300-100,000, preferably 1,000-20,000) produced by heating a mixture of hydrolyzed soybean and RYUGAN (nut shell of Euphoria longan) at 60-200 deg.C. The pressure-sensitive adhesive substance is an acrylic pressure- sensitive adhesive substance [e.g. copolymer of one or more esters such as n-butyl (meth)acrylate, etc., and a vinyl monomer such as (meth)acrylic acid] or a rubber-based pressure-sensitive adhesive substance (e.g. natural rubber, synthetic rubber, etc.). The amount of melanoidin is 0.01-20%, especially 0.1-5% and the ratio of RYUGAN to hydrolyzed soybean used as raw materials for melanoidin is 20:1-1:20. The plaster is used in the form spread over a substrate such as cloth.

Description

[Detailed description of the invention] [Industrial application field] The present invention relates to improvements in plasters made of adhesive substances.

[Prior art]

Conventionally, drugs administered to the integument have been intended to locally act on the integument and underlying tissues thereof, such as bactericides, disinfectants, and skin irritants. However, in recent years, attempts have been made to administer drugs with systemic effects through the integument.

Dermal administration of drugs is carried out, for example, in the form of an adhesive patch in which the drug is mixed into a plaster made of an adhesive substance, but it is also possible to store a drug in a plaster made of an adhesive substance for a long period of time. In this case, the therapeutic effect of the preparation tends to be significantly reduced due to decomposition, volatilization, etc. of the drug.

Incidentally, volatilization and photodecomposition of drugs can be prevented by sealing and blocking light with aluminum laminate packaging, etc., but drugs that are mixed in adhesive pastes, especially phenolic hydroxyl group-containing compounds, amines, etc. Even with aluminum laminated packaging, the decomposition of drugs continues to progress, and many drugs become unusable after being stored for 2 to 3 years. In particular, salicylic acid derivatives such as methyl salicylate and monoglycol salicylate as anti-inflammatory analgesics, skin irritants such as kabsaicin, nonylic acid vanillylamide, and hot pepper extract, ethanolamine antihistamines such as diphenhydramine and its salts, and dl- The content of vitamin E such as α-tocopherol decreases significantly over time.

[Problem that the invention seeks to solve]

Therefore, there is a desire to develop a plaster or adhesive patch made of an adhesive substance that does not easily cause the decomposition of the drug even if it is mixed with the drug, and the present invention is an important technical problem. This was done to solve such technical problems.

[Means for solving problems]

Under these circumstances, the present inventor has conducted various studies and found that a paste made of an adhesive substance contains melanoidin obtained by reacting soybean hydrolyzate with the reducing sugar component in longan. It was discovered that by allowing the drug to be incorporated into the paste, the drug could exist stably without decomposition.

The present invention was completed based on such knowledge,
The present invention relates to a paste comprising a sticky substance containing melanoidin obtained by heating a mixture of soybean hydrolyzate and longan.

The melanoidin referred to in the present invention is as follows.

Examples of melanoidins used in the present invention include:
Particularly preferably used is one obtained by heating soybean hydrolyzate and longan at 60 to 200°C, preferably 120 to 180°C, for 5 minutes to 168 hours, preferably 30 minutes to 24 hours.

The melanoidin obtained in this way is a mixture of substances with various molecular weights, and although no particular means of separation such as purification is required, in the present invention, melanoidin has a molecular weight of 1300 to 100,000, particularly 1000.
20,000 to 20,000 is particularly preferably used.

The blending ratio of longan and soybean hydrolyzate for melanoidin formation is about 20:1 to 1:2o, preferably 5:1 to
l: about 5. Incidentally, as described below, the solvent extract of longan, Type B, can also be used in the present invention, in which case the melanoidin itself may be used in an amount of about 2, and it is preferable to dry and powder the obtained melanoidin.

Longan is generally a member of the family Sapinidae (Sapiaceae).
ndaceae), Longan spp., Longan (Eu-
It refers to dried or semi-dried arils of phoria Iongana (LAMARCK) from which seeds have been removed, but in the present invention, undried ones may also be used. Further, related plants include Litchi chinensis, which belongs to the same wood, and can be similarly used in the present invention. Both of these are high in sugar,
It has traditionally been eaten as a tonic. In the present invention, these are collectively referred to as longan.

These herbal medicines can be used as they are (preferably powdered),
May be used to form melanoidins.

It can also be used as an extract (preferably a dry powder thereof) obtained by extracting the herbal medicine with a polar solvent. In the extraction, a relatively polar solvent (for example, water, ethanol, methanol, acetone, etc., or a mixture thereof) is preferably used. Further, it is preferable to use the n1 eye in powder form.

The extraction time and temperature vary depending on the nature of the solvent used, the degree of cutting of the herbal medicine, etc., but the extraction is usually completed in about 30 minutes to 6 hours at 60°C to boiling iM degree.

The soybean hydrolyzate used in the present invention is obtained by hydrolyzing soybeans with enzymes, acids, alkalis, etc. Specifically, for example, soybeans are subjected to saccharification, proteolysis, and alcohol fermentation through the action of appropriate microorganisms. After the decomposition process,
An example is one obtained by squeezing the product to squeeze out the juice. Suitable microorganisms include, for example, filamentous fungi such as Aspergillus, Mucor, Pericillium, and Rhizopus, yeasts such as Lyria, Mycoderma, and Torula, and bacteria with a high proteolytic ability, Sarcina, and the like. The hydrolysis product mainly contains amino acids, protein decomposition products, and decomposition products such as glucose and dextrin. Before use, it is preferable to remove unnecessary substances such as salt and oil from the juice, and examples of methods for removing them include purification means such as ion exchange resins or reverse osmosis membranes, treatment by heating, and the like.

It is desirable that the soybean hydrolyzate used in the present invention has an amino acid content in the solid content of 0.5% or more, particularly preferably 2% or more.

The amount of melanoidin added to the paste of the present invention may be sufficient to stabilize the drug contained in the paste of the present invention, and is approximately 0.01% to 20%, preferably 0.02%. ~
It is about 10%, and 0.1% to 5% is particularly preferable.

Any adhesive substance that has been conventionally used for patch preparations may be used. Examples include acrylic adhesive substances and rubber adhesive substances.

The acrylic adhesive substance is not particularly limited as long as it has been conventionally used or provided as a plaster for acrylic adhesive patch preparations, such as n-butyl (meth)acrylate, (meth) ) Hexyl acrylate, 2-diethylbutyl (meth)acrylate, isooctyl (meth)acrylate, 2-methoxyethyl (meth)acrylate, 2-ethylhexyl (meth)acrylate, (meth)
Decyl acrylate, dodecyl (meth)acrylate, (
One or more types of (meth)acrylic acid esters such as tridecyl meth)acrylate, (meth)acrylic acid, itaconic acid, maleic acid, maleic anhydride, hydroxyethyl acrylate, which can be copolymerized with the esters, Copolymerization with functional monomers such as hydroxypropyl acrylate, acrylamide, dimethylacrylamide, methylaminoethyl (meth)acrylate, methoxyethyl (meth)acrylate and/or vinyl monomers such as acrylonitrile, vinyl acetate, vinyl propionate. Examples include acrylic compositions such as

Examples of rubber-based adhesive substances include diene-based polymer compounds conventionally used for rubber-based adhesive patch preparations, specifically natural rubber, synthetic rubber, and mixtures thereof. Examples of the synthetic rubber include styrene-isoprene-styrene block copolymer rubber, styrene-butadiene rubber, polybutene rubber, butyl rubber, and silicone rubber.

The adhesive paste also contains third components such as tackifiers such as terpene resins and petroleum resins, liquid paraffin, animal and vegetable oils (for example, olive oil, soybean oil, beef tallow, and tonne fat), and polybutene. , lower isoprene, Wanx, etc. for adjusting adhesive strength and holding power, fillers such as titanium oxide, zinc oxide, aluminum metasilicate, calcium sulfate, calcium phosphate, water, and emulsifiers (for example,
Sorbitan monooleate, sodium lauryl sulfonate), emulsifying aids (eg, magnesium stearate, aluminum stearate), etc. may also be blended.

The plaster of the present invention is formulated into a patch by adding a drug thereto.

There are no particular restrictions on the drug that can be incorporated into the paste of the present invention as long as it can be administered after being made into a tackifier. A stabilizing effect is exerted. Such drugs include, for example, transdermal drugs (although they may be absorbed transdermally with the aid of transdermal absorption aids), topical drugs,
The drug may be any systemic drug), particularly drugs for treating skin diseases, drugs that irritate the skin layer, and drugs for treating indefinite complaints. In particular, the content of phenolic hydroxyl group-containing compounds, amine compounds, etc. is significantly reduced in pastes made of conventional adhesive substances, so the paste of the present invention has particular significance when formulating such drugs. . Examples of compounds containing phenolic hydroxyl groups include salicylic acid derivatives (
monoglycol salicylate, methyl salicylate, etc.)
Vitamin E and its derivatives, cabsaicin, etc. are mentioned, and examples of amine compounds include ethanolamine type antihistamine drugs such as diphenhydramine, ethylenediamine type antihistamine drugs such as chlorpheniramine, and lidocaine. Other medicinal ingredients include l-menthol, dl-camphor,
Cold-sensitive skin irritating drugs such as thymol and d-borneol, non-steroidal anti-inflammatory drugs such as indomexin and diclofenac sodium, fungicides such as chlorhexidine diglyconate and acrinol, capsicum extract, nonylic acid vanillylamide, ginger extract, Examples include crude drugs such as cantharis tincture, cancridin, and other temperature-sensitive skin irritating drugs, and these drugs are also stable in the plaster of the present invention.

In addition, when preparing an adhesive patch using the paste of the present invention, the drug may be added to the adhesive substance first, and then melanoidin obtained by the reaction between soybean hydrolyzate and longan may be added. Needless to say.

Adhesive patch preparations using the plaster of the present invention are usually used by being spread on a support such as cloth or plastic film.

[For production]

The melanoidin blended into the plaster of the present invention has a stabilizing effect on the drug blended into the patch preparation using the plaster.

〔Example〕

EXAMPLES The present invention will be described in more detail below with reference to Examples and Comparative Examples, but the present invention is not limited thereto.

Example 1 43 parts of styrene-butadiene-styrene rubber (indicated by weight, the same applies hereinafter) and 25 parts of natural rosin were kneaded for 20 minutes in a Niguu maintained at 150°C, and the soybean hydrolyzed product obtained in Reference Example 1 was kneaded with this mixture for 20 minutes. 1 part of longan powder and 2 parts of longan dry powder
Flame for a minute, add the dry ingredients, mix and knead for 70 minutes. Next, 5 parts of polybutene, 7 parts of liquid paraffin, 6 parts of titanium oxide powder, and 5 parts of talc were added, and after kneading for 10 minutes, the mixture was cooled to 90°C, and then 5 parts of monoglycol salicylate and 0.5 parts of vanillyl nonylate were added. 0.02 parts of Diphenhydramine and 0.08 parts of diphenhydramine were added, mixed, and applied onto a woven fabric to a thickness of 2 weights to obtain a patch.

Example 2 The soybean hydrolyzate and longan dry powder in Example 1 were
Instead of the one that was smoked for 0 minutes and dried, 2 parts of longan water extract and 20 parts of the soybean hydrolyzate were heated at 100°C for 4 hours and dried, and the rest was as in Example 1.
A patch was obtained in the same manner as above.

Comparative Example A In Example 1, the soybean hydrolyzate and longan dry powder were
A patch was obtained in the same manner as in Example 1, except that the mixture was simmered for 0 minutes and dried.

Experimental Example 1 The patches prepared in Example 1.2 and Comparative Example A were sealed from light with an impermeable substrate laminated with aluminum, and stored at 40°C for 3 months. The amount of decomposed active ingredient contained therein was measured by liquid chromatography. I looked it up. The calculated values are shown in Table 1 below, taking the theoretical value as 100%.

(Margin below) Table 1 Example 3.4 A patch was obtained by repeating the operation of Example 1 except for using 2-ethylhexylethyl acrylate polymer instead of the styrene-butadiene-styrene rubber in Example 1.2. Ta. (Example 3: used the one that was cultivated for 10 minutes and dried, Example 4: used the one that was heated at 100°C for 4 hours) Comparative Example B In place of the styrene-butadiene-styrene rubber in Comparative Example A, 2 - Using ethylhexylethyl acrylate polymer, and adding soybean hydrolyzate and longan dry powder to 1 part
Comparative example A except that sushi is made for 0 minutes and dried chichino is not used.
The above procedure was repeated to obtain a patch.

Experimental Example 2 The formulations of Example 3.4 and Comparative Example B were tested according to Experimental Example 1, and the results are shown in Table 2.

Table 2 Examples 5 to 11 The drug in Example 1 was mixed with 5 parts of monoglycol salicylate (Example 5) and 0.0 parts of vanillyl nonylate acid.
02 parts (Example 6), 0.08 parts of diphenhydramine (
Example 7), 5 parts of methyl salicylate (Example 8), 0.02 part of kabsaicin (Example 9), 1 part of indomethacin (Example 10), 0.1 part of betamethacin valerate (Example 11) alone. A patch was obtained which was treated in the same manner as in Example 1 except for this.

Comparative Example C-1 A patch was obtained in the same manner as in Examples 5 to 11, except that the soybean hydrolyzate and longan dry powder in Examples 5 to 11 were fielded for 10 minutes, and the dried powder was not used. (Comparative example C
・・Monoglycol salicylate, Comparative Example D・・Vanilylamide nonylate, Comparative Example E・・Diphenhydramine, Comparative Example F・・Methyl salicylate, Comparative Example G・・Kabsaicin, Comparative Example H・・Indomethacin, Comparative Example ■・・Kichi Betamethacin grass acid) Experimental Example 3 The formulations of Examples 5 to 11 and Comparative Examples C to ■ were tested according to Experimental Example 1, and the results are shown in Table 3.

(Margin below) Table 3 Experimental Example 4 When the formulations of Example 1 and Example 2 were applied to human skin and left for 6 hours, the skin was observed, and no side effects such as redness and rash were observed in either case. It was proved that the plaster of the present invention can be safely administered.

Reference Example 1 100g of soybeans were heated in boiling water for 6 hours, kneaded, and then mixed with 6N hydrochloric acid in a shielded tube at 120℃ for 2 hours.
Hydrolysis was carried out by heating for 4 hours, and the obtained product was neutralized with sodium hydroxide and used.

Reference Example 2 To the soybean hydrolyzate obtained in Reference Example 1, 100 g of Longan was heated and extracted with 12 parts of water (boiled for 3 hours) and liquid 61 was added, boiled and heated for 1 hour, and then dried. The dried product is heated at 160°C for 2 hours to form a dry powder.

〔effect〕

As is clear from the above table, by adding melanoidin obtained by heating a mixture of soybean hydrolyzate and longan to an adhesive paste, drug concentration in a patch using the paste can be improved. Oral stability is increased.

Therefore, preparations using the present invention plaster can withstand long-term storage;
It is possible to avoid the loss of preparations due to decomposition of crude drugs, which was seen in the past.

Claims (3)

[Claims] (1) A paste comprising a sticky substance containing melanoidin obtained by heating a mixture of soybean hydrolyzate and longan. (2) Amino acid content in the solid content of soybean hydrolyzate is 0
．． The plaster according to claim (1), which has a content of 5% or more. (3) The paste according to claim (1) or (2), wherein the melanoidin is obtained by heating a mixture of soybean hydrolyzate and longan at 90 to 200°C. .