Niigata Dent. J. 39（1）：25 － 28,

2009

25

－ ORIGINAL ARTICLE －Effect of 6-month administration of Cevimeline hydrochloride on salivary flow rateand ｓ alivary components in primary Sjögren’s syndrome patients
Saori Funayama1）, Kayoko Ito2）, Yasumasa Hitomi1）, Shihoko Sakuma3）,
Satoshi Ito4）, Shuichi Nomura5）, Atsuko Igarashi6）**
1)

Division of Dysphagia Rehabilitation, Course for Oral Health Science, Niigata University Graduate School of Medical and Dental Sciences
2)
3)

4)

Geriatric Dentistry, Niigata University Medical and Dental Hospital

Preventive Dentistry Clinic , Department of Oral Health Control, Niigata University Medical and Dental Hospital

Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba5)

Division of Comprehensive Prosthodontics, Course for Oral Health Science, Niigata University Graduate School of Medical and Dental Sciences6)

Department of Oral Health and Welfare Science, Faculty of Dentistry, Niigata University

一次性シェーグレン症候群患者の唾液分泌量と唾液成分に対する塩酸セビメリン投与後６ヶ月の効果
船山さおり 1），伊藤加代子 2），人見康正 1），佐久間汐子 3），伊藤１）聡 4），野村修一 5），五十嵐敦子 6）新潟大学大学院医歯学総合研究科

新潟大学医歯学総合病院

加齢歯科診療室３）新潟大学医歯学総合病院

予防歯科診療室

４）５）

摂食・嚥下リハビリテーション学分野

２）

筑波大学大学院人間総合科学研究科

新潟大学大学院医歯学総合研究科
６）

包括歯科補綴学分野

新潟大学歯学部口腔生命福祉学科
平成 21 年３月６日受付

福祉学講座

４月６日受理Key Words : Cevimeline hydrochloride, primary Sjögren’s syndrome, Saliva
Abstract：The aim of this study was to clarify pre- and post-cevimeline hydrochloride administrative changes ofsalivary flow rate and salivary components in primary Sjögren’s syndrome (SS) patients. Twelve females whowere diagnosed with primary SS were subjects in this study. Thirty milligrams of cevimeline hydrochloride wasadministered 3 times daily for 6 months. Whole stimulated saliva was collected from patients before and afteradministration. MMP(matrix metalloproteinase)-9 was measured by the sandwich-ELISA (enzyme-linkedimmunosorbent assay) method. The levels of Na+, Cl- and K+ ions were measured by the ISE (ion-selectiveelectrode) method. The level of Ca2+ ion was measured by the OCPC (ortho-cresolphthalein-complexone) method
and amylase activity was determined by the enzyme coupling method. Whole stimulated saliva secretion wassignificantly higher (p ＝ 0.034) after administration. Na+,Cl-,Ca2+ ions and MMP-9 levels were not different afteradministration. Amylase activity(p ＝ 0.105)and K+ ion level(p ＝ 0.105)decreased but not significantly afteradministration. Therefore, Cevimeline hydrochloride at a dosage of 30 mg, 3 times daily may improve some
symptoms of xerostomia in patients with primary SS, though there was no change of salivary components.

**Correspondence author: Atsuko Igarashi－ 25 －26

新潟歯学会誌

39（1）
：2009

抄録：この研究の目的は一次性シェーグレン症候群患者（pSS）の唾液分泌量と唾液成分に対する塩酸セビメリン投与前後の変化を調べることである。この研究の対象者は一次性 p ＳＳ患者 12 人であった。６ヶ月間１日３回 30mgの塩酸セビメリンを投与した。試料としての全唾液は投与前後に集めた。Matrix Metalloproteinase-9（MMP －９）
は sandwich-ELISA(enzyme-linked immunosorbent assay) 方 法 で 測 定 し た。Na，Cl と K イ オ ン は OCPC(orthocresolphthalein-complexone) 方法で測定し，アミラーゼ活性は Enzyme coupling 法で測定した。その結果，全刺激唾液は投与後で有意に増加した（P ＝ 0.034）。Na，Cl，Ca イオンと MMP-9 レベルは投与後で変化がみられなかった。
アミラーゼ活性（P ＝ 0.105）と K イオンレベル（P ＝ 0.105）は投与後に減少傾向を示したが , 有意差は認められなかった。それゆえ，塩酸セビメリン 30mg の１日３回投与によって，一次性シェーグレン症候群患者（pSS）の唾液成分は変化しなかったが，口腔乾燥症状は改善する可能性が示された。

primary SS 2）. Before administration of cevimeline

Introductionhydrocloride, there were twelve female patients[average age 55.25±14.40 years (mean±S.D.)] with

Sjögren’s syndrome(SS)is a systemic chronic

primary SS who had been referred to Niigata

autoimmune disease, characterized by symptoms ofUniversity, Medical and Dental Hospital. On the otherdry mouth and dry eyes, and can be primary or

hand, the control subjects were twenty one females

secondary to connective tissue diseases such as[average age 54.00±9.76 years (mean±S.D.)]. All

rheumatoid arthritis, systemic lupus erythematosus,

patients and control subjects gave informed consent

polymyositis, and systemic sclerosis. Furthermore, it isand the Declaration of Helsinki (September 1989) was

said that SS is divided into primary and secondary

followed throughout the study. Statistical analysis wasclasses according to symptoms and more prevalent in

performed only on the patients in which enough saliva

climacteric women. Pharmacotherapeutic approaches

was available for measurements at all stages (beforeto xerostomia in SS include lubricating oral mucosa

treatment, 1 month after treatment and 6 months afterwith saliva substitutes, treatment withtreatment).

immunosuppressive drugs and stimulating salivary

3. Saliva sample

gland activity with muscarine agents. Cevimeline

Patients were administered with 30 mg ofhydrochloride(Saligren®, Evoxac®)is an acetylcholine

Cevimeline hydrochloride 3 times daily for 6 months.

analogue with high affinity for the muscarinic M3

Whole saliva was collected during stimulation byreceptor located on lacrimal and salivary glandchewing paraffin for 10 min from patients between 9:00

epithelium and is an orally administered drug thatam and 12:00 noon before administration as well as

relieves the symptoms in patients with SS . In thisafter administration at their first- and sixth-monthstudy, we investigated the effect of cevimeline

visits.

1）hydrochloride (Saligren®, Evoxac®) administration on

The saliva of control subjects was collected in thesalivary flow rate and salivary components in patientssame way as the patients. Immediately after thewith primary SS.

collection, the saliva was centrifuged at 12,000 rpm for5 min at 4℃ to remove the precipitate. The

Materials and Methods

supernatant was frozen quickly at -80℃ until use. The
patients were asked not to eat on the day ofexamination. Except saliva flow rate measurement,

1. Materials
Materials were as follows: Cevimeline hydrochloride

the determination item numbers were not the same in(Saligren® Nippon Kayaku Inc. Japan; Evoxac®

all stages. The reason for this was the differences in

Daiichi-Sankyo Pharmaceutical Company Japan); MMP-

the volume of saliva secretion among individuals.

9 enzyme-linked immunosorbent assay (ELISA) system

Therefore, for some patients, saliva volume was notkit (Amersham Bioscience, USA).

enough to measure all items. The priority for

2. Subjects

measurement was MMP-9 ELISA assay.

The patients were diagnosed according to thepreliminary classification criteria proposed by the

4. One-step sandwich EIA system for MMP-9 ELISA
assay

Japanese Study Group on Diagnostic Criteria for－ 26 －MMP-9 (Amersham Pharmacia Biotech Inc.) was