JP2008031079A - Medicine for suppressing symptom accompanying with pollinosis - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a medicine for suppressing various symptoms of pollinosis in nasal cavity mucosa and eye mucosa, and excellent in both of the instantaneous onset and lasting property of medical benefits. <P>SOLUTION: This medicine for suppressing the various symptoms of pollinosis in nasal cavity mucosa and eye mucosa by a medicine for suppressing the symptoms accompanying the pollinosis characterized by containing crotamiton as an active ingredient, and also excellent in both instantaneous effectiveness and lasting property of the medical benefits is provided. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a drug for suppressing various symptoms of hay fever in the nasal mucosa and ocular mucosa.

  Hay fever is considered to be an allergic disease caused by pollen. Symptoms of hay fever are nasal mucosa and eyes such as nasal inflammation in the extranasal nasal mucosa (nasal mucosa) such as paroxysmal sneezing, runny nose and itchiness, and itching of the ocular mucosa (particularly the eyelid conjunctiva). Specific examples include various symptoms in the mucous membrane.

  For allergic diseases such as hay fever, various drugs have been proposed to suppress various symptoms in the nasal mucosa and ocular mucosa. For example, for rhinitis containing a vasoconstrictor and sodium cromoglycate. Nasal drops (Patent Document 1) and eye drops have been proposed.

Japanese Patent Application No. 10-1442

  The nasal drops for rhinitis shown in Patent Document 1 requires a certain amount of time to produce medicinal effects that suppress various symptoms of allergic diseases such as hay fever, and are not necessarily sufficient in terms of immediate effect. . In addition, the nasal drops for nasal inflammation are used by being sprayed into the nasal cavity and may not be sufficiently adhered to the nasal mucosa, so that it is not sufficient in terms of sustained medicinal effects. The same applies not only to nasal drops for rhinitis but also to eye drops, and a drug that can effectively and effectively suppress various symptoms of hay fever that occur in the nasal mucosa and ocular mucosa is desired. ing.

  The present inventors have found that crotamiton, which has a relieving effect on the symptoms of itching in the skin, effectively relieves and improves pruritus associated with hay fever in mucous membranes such as nasal mucosa and ocular mucosa. The invention has been completed.

  An object of the present invention is to provide a drug for suppressing various symptoms of hay fever in the nasal mucosa and ocular mucosa, which is excellent in both immediate action and sustainability of the drug effect.

  The present invention is characterized in that (1) a drug for suppressing symptoms associated with hay fever, characterized by containing crotamiton as an active ingredient, and (2) an antiallergic agent is further added. The gist is the drug according to (1) or (2) above, wherein the drug according to (1) and (3) the dosage form is an ointment.

  According to the present invention, crotamiton is contained as an active ingredient in a drug for suppressing symptoms associated with hay fever (sometimes referred to as a hay fever drug or a drug), and this drug is contained in the nasal mucosa and ocular mucosa. By applying, the symptoms of the nasal mucosa and ocular mucosa associated with hay fever can be immediately suppressed and alleviated. According to the present invention, various symptoms of hay fever on the ocular mucosa (particularly the eyelid conjunctiva) can be quickly suppressed and alleviated by applying this hay fever drug to the ocular mucosa. By simply applying it to the eyelids, it becomes possible to suppress and alleviate various symptoms of hay fever that occur in the ocular mucosa.

  Furthermore, according to the present invention, the anti-allergic agent may be added to the hay fever drug as an active ingredient having an action different from that of crotamiton on the nasal mucosa and ocular mucosa. After the symptoms of hay fever were suppressed and alleviated with immediate effect, the effects of antiallergic drugs such as sodium cromoglycate gradually emerged over time, and the symptoms of hay fever were suppressed. The state can be further sustained. That is, according to the present invention, the anti-allergic agent is further added to the drug, and the drug is a combination of crotamiton and the anti-allergic drug. In particular, various symptoms associated with hay fever in the eyelid conjunctiva) can be suppressed.

  According to the present invention, the dosage form of the drug may be an ointment (however, when the drug is administered to the eye, it is an ointment), in which case the drug is a spray. Compared with some cases, after application, the nasal mucosa and ocular mucosa can be reliably maintained in a state where the drug adheres, and active ingredients such as crotamiton and antiallergic drugs contained in this drug It is possible to suppress the absorption of the active ingredient from the surface and the surface of the ocular mucosa to the body excessively, make the absorption of the active ingredient into the body at an appropriate speed, and allow the drug to have sustained release. Thus, the drug can be made more excellent in sustainability and can be used efficiently.

  The drug of the present invention contains crotamiton as an active ingredient. It is preferable that crotamiton is blended in an amount of 1% by weight or more based on the weight of the drug of the present invention from the viewpoint of obtaining an effect of suppressing various symptoms of hay fever with sufficient immediate effect.

  The drug of the present invention may contain an antiallergic drug. Antiallergic agents include tranilast, sodium cromoglycate, amlexaxnos, repirinast, mediator release inhibitors such as ibudilast, tazanolast, pemirolast, antihistamines such as ketotifen fumarate, azelastine hydrochloride, oxatomide, mequitazine, terfenadine, etc. Specific examples can be given. Considering that antiallergic drugs can penetrate and be absorbed into the body from the skin site such as eyelids, antiallergic drugs are preferably ketotifen fumarate, azelastine hydrochloride, oxatomide, mequitazine, terfenadine, etc. , Ketotifen fumarate is preferred. If the antiallergic agent can penetrate into the body from the skin site, the medicinal effect can be obtained effectively even when the drug is applied not only to the mucosal site but also to the skin site.

  The medicament of the present invention may be configured such that the dosage form is an ointment. In that case, as an ointment base used in an ointment, a base that can be used in a normal ointment can be appropriately selected and used. Vaseline, white petrolatum (ophthalmic petrolatum, propetol), plastibase, purified lanolin, Specific examples include carboxymethyl cellulose, carboxymethyl polymer, liquid paraffin, beeswax, glycerin and the like.

  When the drug is an ointment, crotamiton, an antiallergic drug, or the like is added as an active ingredient to the ointment base to form the drug of the present invention.

  In addition, additives, such as a moisturizing agent and antiseptic | preservative, may be mix | blended with the chemical | medical agent of this invention. Additives can be appropriately added in a blending amount that does not interfere with the efficacy of the active ingredient of the drug.

  Next, the chemical | medical agent of this invention is demonstrated in detail, showing an Example concretely.

Example 1
White petrolatum (Propet) manufactured by Maruishi Pharmaceutical Co., Ltd. is used as the ointment base, and clotamiton (Sigma Aldrich Co., crotamiton) and white petrolatum are mixed in the blending amounts shown in Table 1 to form an ointment. Got. The obtained ointment corresponds to the drug of the present invention.

(Table 1)

  Five adults with various symptoms of hay fever in the nasal mucosa and ocular mucosa were selected as subjects, and the drug (ointment) obtained above was applied according to each subject's symptoms, and the nasal mucosa associated with hay fever The efficacy of the drug was measured and evaluated for various symptoms and symptoms of the ocular mucosa.

  In the evaluation of the efficacy of drugs, the various symptoms of nasal mucosa are evaluated for three symptoms: itchiness, sneezing, and runny nose. The itch symptoms were evaluated.

  In measuring the efficacy of the drug for various symptoms of the nasal mucosa, the itchiness has symptoms of itchiness at the time of starting the measurement of the efficacy (at the start of the efficacy measurement) among 5 adult subjects. Four subjects were measured, and similarly, for sneezing, four subjects with sneezing symptoms were measured, and for runny nose, two subjects with nasal symptoms were measured. .

  Further, when measuring the drug efficacy for the symptoms of the ocular mucosa, measurement was performed on 4 subjects who had itching of the eyelid conjunctiva as a symptom at the time of starting the efficacy measurement among 5 adults as subjects.

"Evaluation of medicinal effects"
<Symptoms of nasal mucosa>
About 200 mg of the drug was placed on the tip of a sterilized cotton swab, and the drug adhered to the swab was applied to each subject from the nasal limit to a position of about 1.5 cm in the back from the nasal mucosa. The drug was applied to each of the left and right nasal mucosa. Next, the presence or absence of various symptoms of the nasal mucosa associated with hay fever was measured and investigated over time after application of the drug for each measurement subject. Then, for each nasal mucosal symptom associated with hay fever, the number of subjects (symptoms) who have developed the target symptom among the measurement subjects is counted sequentially over time. The time course of was examined. In addition, after the chemical | medical agent was apply | coated and the measurement of the medicinal effect was started, until the measurement was complete | finished, the chemical | medical agent was not applied further.

The presence or absence of various symptoms of hay fever after application of the drug (after the start of medicinal effect measurement) is determined when the subject feels the various symptoms more than a predetermined standard and there is a hay fever symptom. It was carried out by. That is, for the symptoms of itching, it is determined that there is an itching symptom associated with hay fever if you feel itching after starting the medicinal effect measurement, and for the symptoms of sneezing, 5 If sneezing more than once, it is determined that there is a sneezing symptom associated with hay fever. When biting, it was determined that there was a runny nose associated with hay fever. Here, to determine the symptoms of sneezing associated with hay fever, “Masao Enomoto, Satoshi Fujimura, Jinya Fukui,“ Improving the quality of hay fever treatment—20 medical navigations to physicians ”published in 2000, The criteria for diagnosing hay fever as described in Medical School, page 1 were used.
The results are shown in Table 2 for each case where the symptoms of hay fever in the nasal cavity are itchiness, sneezing, and runny nose.

<Ocular mucosa symptoms>
The medicinal efficacy of the ocular mucosa was measured by measuring the itch symptoms in the eyelid conjunctiva as follows.

  First, the drug was administered to the eye part of the measurement subject who had itch symptoms of the eyelid conjunctiva. Examples of drug administration methods for dealing with itching of the eyelid conjunctiva include a method in which the drug is applied to the eyelid conjunctiva (ie, mucosal site) and a method in which the drug is applied to the eyelid (ie, skin site). In 1, a method of applying a drug to the eyelid conjunctiva was used. Specifically, about 50 mg of the drug was applied to the inner and outer eye corners of the eye mucosa and the position of the upper eyelid conjunctiva along the boundary with the eyelid. A sterilized cotton swab was used for drug application.

  Subsequently, the presence or absence of symptom of itching (pruritus sensation) of the eyelid conjunctiva was investigated for each subject over time after drug application. Thus, the number of subjects (number of symptomatic subjects) who were symptom of itch in the eyelid conjunctiva among the measurement subjects was sequentially counted over time, and the time transition of the number of symptomatic subjects was examined. . In the measurement, after the drug was applied to the eyelid conjunctiva and the measurement of the medicinal effect was started, no additional drug was applied until the measurement was completed.

  Determination of the presence or absence of ocular mucosal symptoms after application of the drug was performed by determining the presence or absence of itching of the eyelid conjunctiva. Judgment of the presence or absence of itch of the eyelid conjunctiva is determined after the start of medicinal effect measurement, when itching the eyelid conjunctiva and scratching the site that causes itching, it is determined that there is a symptom of ocular mucosa associated with pollinosis Made by. The results are shown in Table 2.

表中各欄において、表に向かって右側の数字は、測定対象者の人数を示し、表に向かって左側の数字は、有症者数を示す。 (Table 2)

In each column in the table, the number on the right side of the table indicates the number of persons to be measured, and the number on the left side of the table indicates the number of affected persons.

Example 2
As an antiallergic agent, cromoglycate sodium (Cromolyn sodium, manufactured by Sigma-Aldrich Co., Ltd.) is highly safe and has no excessive absorption in the body. And white petrolatum as an ointment base were mixed to obtain an ointment as a medicine of the present invention. In addition, the same thing as Example 1 was used for crotamiton and white petrolatum.

  Using the obtained ointment, in the same manner as in Example 1, the efficacy of various symptoms of the nasal mucosa associated with hay fever and symptoms of the ocular mucosa associated with hay fever was evaluated. That is, in the same manner as in Example 1, five adults having various symptoms associated with hay fever were selected as subjects, and the ointment obtained above was applied according to each subject's symptoms. The medicinal efficacy of the ointment for each measurement subject was measured, the time course of the number of affected persons was examined, and the medicinal efficacy of the ointment was evaluated. Table 3 shows the results of measuring the medicinal efficacy of the ointment. In this Example 2, the number of measurement subjects was 3 people, 3 people, 4 people, 3 people for the symptoms of itchiness of the nasal mucosa, sneezing, runny nose, and eye mucosa, respectively. Name.

表中各欄において、表に向かって右側の数字は、測定対象者の人数を示し、表に向かって左側の数字は、有症者数を示す。 (Table 3)

In each column in the table, the number on the right side of the table indicates the number of persons to be measured, and the number on the left side of the table indicates the number of affected persons.

Comparative Example 1
As shown in Table 1, only white petrolatum was used to make an ointment, and in the same manner as in Example 1, the medicinal effects on various symptoms of the nasal mucosa and ocular mucosa associated with pollinosis were evaluated.

  In this case, in the same manner as in Example 1, five adults having various symptoms associated with hay fever were selected as subjects, the ointment was applied according to the symptoms of each subject, and each measurement target for various symptoms of hay fever was measured. The efficacy of the ointment was measured by measuring the medicinal effect of the ointment on the elderly, examining the time course of the number of affected persons. Table 4 shows the results of measuring the medicinal efficacy of the ointment. In this Comparative Example 1, the number of measurement subjects was 4 people, 4 people, 3 people, 4 people for nasal mucosal itchiness, sneezing, runny nose, and ocular mucosal symptoms, respectively. Name.

表中各欄において、表に向かって右側の数字は、測定対象者の人数を示し、表に向かって左側の数字は、有症者数を示す。 (Table 4)

In each column in the table, the number on the right side of the table indicates the number of persons to be measured, and the number on the left side of the table indicates the number of affected persons.

  In the drugs obtained in Examples 1 and 2, compared to the ointment of Comparative Example 1, after the start of measurement of medicinal effects, the time required until a decrease in the number of symptomatic people is observed is short and excellent in immediate effect. It is shown. Furthermore, in the drugs obtained in Examples 1 and 2, after a decrease in the number of affected persons was observed, there was a time interval until the number of affected persons started to increase, and it was shown that the medicinal effects are persistent. ing. Among Examples 1 and 2, in particular, the drug obtained in Example 2 is more excellent in immediate effect and sustainability.

Claims (3)

A drug for suppressing symptoms associated with hay fever, comprising crotamiton as an active ingredient. The drug according to claim 1, further comprising an antiallergic drug. The medicine according to claim 1 or 2, wherein the dosage form is an ointment.