JP5336527B2 - Lidocaine-containing jelly - Google Patents

Description

The present invention relates to a jelly agent containing lidocaine .

It is well known that local anesthetic drugs are used in the mouth for dentistry.
Among local anesthetics, lidocaine and the like are used for throat anesthesia when using a gastrocamera, and are also used as drugs for tachycardia.

  On the other hand, in recent years, it is known that a preparation obtained by jelly-forming lidocaine, which is a local anesthetic drug, in a hospital prescription with carrageenan is used for pain relief of stomatitis in cancer patients.

  Cancer patients are expected to be treated or prolong their lives due to the development of anticancer drugs, but on the other hand, they often feel mental and physical distress due to side effects of anticancer drugs caused by chemotherapy. Relieving mental and physical distress due to side effects can not only increase the quality of life of cancer patients, but also reduce the burden on treatment personnel such as doctors and caregivers.

  As a side effect of such an anticancer agent, intractable severe stomatitis is known. From the beginning of chemotherapy, dry mouth, abnormal taste, pain, etc. have appeared, causing problems such as deterioration of nutritional status and interruption of chemotherapy. Local anesthetic drugs are effective as a countermeasure against such stomatitis pain.

  However, local anesthetic drugs are substances that have a strong bitterness, as typified by lidocaine and ethyl paraaminobenzoate, and are problematic because they have a strong discomfort when taken as an oral or oral preparation. When the preparation concentration of the local anesthetic drug is so low that there is no bitter discomfort, the effect as a local anesthetic drug is hardly seen. Therefore, when it is used for oral and oral use, it is used at a high concentration of 2% or more, and many people take it with an unpleasant bitterness.

  As a countermeasure against such unpleasant bitterness, the present inventors have the knowledge that bitterness can be completely masked by adding a weak acid to the local anesthetic drug at a certain ratio or more. In addition, oral dosage forms such as liquids, ointments, jellies, gummi, dry syrups, powders, fine granules, etc. can be taken as dosage forms for preparations containing local anesthetic drugs. When it is used as pain relief for stomatitis, the jelly agent can be administered locally, and the local anesthetic drug can be administered by applying the jelly agent to the affected area in addition to ease of handling and good touch in the mouth. It is optimal because it reduces the side effects of biting the tongue and strong discomfort that occurs during anesthesia in the mouth, and also allows you to enjoy a meal.

  By the way, when a local anesthetic drug is used for oral and oral use, it is generally used at a high concentration of 2% or more. Therefore, when a local anesthetic drug is used at a high concentration, a weak acid for masking the bitter taste is also used at a high concentration. However, when a weak acid, particularly an organic acid such as citric acid is blended at a high concentration in the jelly agent, water separation from the jelly agent occurs during long-term storage. When water separation occurs in jelly preparations, liquids spilled while taking the medicine, problems with administration of local anesthetic drugs to the local area, which is an advantage of jelly preparations due to the water separation liquid, and gel formation due to water separation It becomes stiff and the release of the drug is weak or difficult to take, causing many problems.

  The problem to be solved by the present invention is to provide a preparation that solves the above-mentioned problem of water separation from the jelly agent while overcoming discomfort such as bitterness that is a problem in the jelly agent containing a local anesthetic drug.

  As a result of intensive studies, the present inventors have found that water separation from the jelly agent is improved by mainly using phosphoric acid as a weak acid for overcoming the bitter taste of a local anesthetic drug. Thus, the present invention was completed.

  That is, the local anesthetic drug-containing jelly of the present invention is characterized by blending phosphoric acid or a pharmaceutically acceptable salt thereof or a mixture thereof.

  The above-mentioned jelly agent containing a local anesthetic drug is characterized in that the local anesthetic drug to be mixed is lidocaine or a pharmaceutically acceptable salt thereof or a mixture thereof.

  The above-mentioned jelly agent containing a local anesthetic drug contains 1% or more of the local anesthetic drug to be used.

The lidocaine- containing jelly agent of the present invention improves bitterness by blending phosphoric acid as a weak acid, and significantly reduces water separation from the jelly agent, which is a problem. In particular, a jelly agent is an optimal dosage form for alleviating the pain of stomatitis that occurs as a side effect of cancer chemotherapy, and is highly desired. Therefore, the present invention overcoming such problems at the time of developing a jelly agent is extremely excellent because it can greatly contribute to the improvement of the patient's QOL.

  The local anesthetic drug according to the present invention is not particularly limited, but examples thereof include lidocaine, ethyl paraaminobenzoate, oxybuprocaine, tetracaine, procaine, diethylaminoethyl parabutylaminobenzoate, and the like, or pharmaceutically acceptable salts thereof. And may be a mixture thereof. Particularly preferred is lidocaine.

  The jelly agent containing a local anesthetic drug of the present invention has a particularly preferable effect by adding phosphoric acid or a pharmaceutically acceptable salt thereof or a mixture thereof. Although it does not specifically limit as phosphoric acid or its pharmacologically acceptable salt, For example, phosphoric acid, sodium hydrogen phosphate, trisodium phosphate, dipotassium phosphate, potassium dihydrogen phosphate, calcium dihydrogen phosphate, diphosphoric acid phosphate Examples thereof include sodium hydrogen and sodium dihydrogen phosphate monohydrate. In particular, phosphoric acid and sodium hydrogen phosphate are preferable.

Moreover, the jelly agent containing a local anesthetic drug can be added if a weak acid other than the phosphoric acid of the present invention is contained in a small amount.
Examples of the inorganic weak acid that can be blended include carbonic acid or a salt thereof.
Examples of organic acids that can be blended include malic acid, citric acid, tartaric acid, ascorbic acid, succinic acid, fumaric acid, maleic acid, gluconic acid, glucuronic acid, and salts thereof. Moreover, you may mix | blend these mixtures irrespective of an inorganic acid and an organic acid. Preferably, phosphoric acid, sodium hydrogen phosphate, citric acid, sodium citrate is mixed, and particularly preferably, phosphoric acid, sodium hydrogen phosphate, sodium citrate, and the like.

  The jelly agent containing a local anesthetic drug of the present invention can form a gel jelly agent by using a gelling agent. The gelling agent is not limited as long as it is pharmaceutically acceptable, for example, sodium alginate, agar, agar powder, gelatin, pectin, xanthan gum, carob bean gum, carrageenan, tragacanth, tragacanth powder, guar gum, pullulan, tamarind seed gum , Curdlan, gellan gum, glucomannan and the like. Carrageenan, agar powder, xanthan gum and carob bean gum are particularly preferable.

  Sweeteners can be added to the formulations of the present invention. Examples of the sweetener include aspartame, saccharin, sodium saccharin, stevia, thaumatin, erythritol, sorbitol, xylitol, glycerin, dipotassium glycyrrhizinate, and a mixture thereof. Preferable sweeteners include aspartame, saccharin, saccharin sodium and stevia.

  In the preparation of the present invention, a pharmaceutically acceptable non-toxic and inert additive can be added. Examples of these additives include corn starch, potato starch, sucrose, mannitol, xylitol, sorbitol, talc, kaolin, calcium hydrogen phosphate, calcium sulfate, calcium carbonate, crystalline cellulose and other excipients, magnesium stearate, Lubricants such as calcium stearate, disintegrants such as calcium carboxymethylcellulose, sodium carboxymethylcellulose, low-substituted hydroxymethylcellulose, polyethylene glycol, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, gelatin, methylcellulose, gum arabic powder, polyvinyl alcohol Binders, etc., other thickeners, colorants, flavoring agents, adsorbents, preservatives, stabilizers, wetting agents, antistatic agents, H adjusting agents and the like.

  Moreover, the jelly agent containing the local anesthetic drug of the present invention can be used as an ice ball after being frozen, and can be effectively used for pain relief such as stomatitis.

  Hereinafter, the present invention will be described more specifically with reference to examples and experimental examples. However, the present invention is not necessarily limited thereto. In addition, the value of the compounding quantity in a present Example and a comparative example is all the mass%.

(Test Example 1)
According to the mixing ratio in Table 1, a jelly agent containing lidocaine hydrochloride as a local anesthetic was prepared. That is, the raw materials shown in Table 1 were dispersed or dissolved in purified water and then dissolved by heating. After cooling to room temperature, a local anesthetic drug-containing jelly was prepared.

Using Formulation Examples 1 to 3 prepared according to Table 1, the presence or absence of water separation from the jelly agent was confirmed.
The jelly agents of Formulation Examples 1 to 3 were each filled in an aluminum container whose inner surface was polyethylene-coated, and stored at room temperature for 6 months. After storage, the presence or absence of water separation from the jelly agent was observed. The results are shown in Table 2.

  Moreover, the presence or absence of the bitter taste of each of Preparation Examples 1 to 3 was confirmed. The bitterness was confirmed by a sensory test by a healthy person. Bitterness discomfort was determined when about 1 g of each of Formulation Examples 1 to 3 was included in the mouth. Table 3 shows the presence or absence of bitterness. At the same time, the citrate ion concentration and phosphate ion concentration of Preparation Examples 1 to 3 are shown in Table 3.

From the results in Tables 2 and 3, the jelly agent containing a high concentration of citrate ions as in Preparation Example 3 generates water separation but the bitterness is improved, and the concentration of citrate ions is lowered as in Preparation Example 2. Then, although water separation was suppressed, it was shown that the bitterness which a local anesthetic drug has cannot be improved.
However, as shown in the results of Preparation Example 1, even when the citrate ion concentration is kept low, the bitterness of the local anesthetic drug can be suppressed by adding phosphate ions. In this case, it was shown that water separation does not occur.

(Formulation Example 4) Preparation of Lidocaine Hydrochloride-Containing Jelly Agent Lidocaine hydrochloride 2.0, sodium citrate 0.9, phosphoric acid 0.5, sodium hydrogenphosphate dodecahydrate 1.78, saccharin sodium 0.5, azulene sulfone Sodium phosphate 0.008, dipotassium glycyrrhizinate 0.5, polyvinyl alcohol 0.3, polyethylene glycol 5.1, glycerin 13.3, concentrated glycerin 4.2, propylene glycol 4.6, carrageenan 0.7, xanthan gum 0 .3, Kanteng powder 0.17, Calob bean gum 0.05, Preservative appropriate amount was dissolved or suspended in purified water adjusted to 100 in total, dissolved by heating and cooled to room temperature to prepare 2% lidocaine jelly hydrochloride .

Relieving the pain of stomatitis that occurs as a side effect of cancer chemotherapy is an important issue for improving QOL of patients, and lidocaine is effective. A jelly agent is optimal as a dosage form of a preparation containing lidocaine, but depending on the weak acid added to overcome the unbearable bitterness of lidocaine, water separation occurs from the jelly agent, causing problems when taken.
By utilizing the present invention, it is possible to provide a lidocaine- containing jelly agent having no water separation and having overcome bitterness.

Claims (1)

A lidocaine-containing oral or oral jelly bitterness improving agent comprising phosphoric acid or a sodium salt thereof or a mixture thereof as an active ingredient ,
The amount of the phosphoric acid or its sodium salt or a mixture thereof is an amount of 90 mM as a phosphate ion concentration as an amount that does not cause water separation after storage at room temperature for 6 months,
The amount of citrate ion concentration is 30 mM as an amount that does not cause water separation after storage at room temperature for 6 months.
The bitterness improving agent of the lidocaine containing oral or oral jelly agent characterized by the above-mentioned.