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골흡수억제제

[약 이야기] 골다공증 치료제가 뼈를 녹인다고요? :: 중앙일보헬스미디

메디칼타임즈 : 골다공증약 포스테오 삭감 주의보나이가 가장 큰 변

  1. 골밀도 검사를 통해 확인되는 티 수치(T-scores)로 판단합니다. 수치가 -1 이상이면 정상이며, -1∼-2.5 사이면 골감소증으로 분류합니다. 수치가 –2.5 이하일 경우 골다공증으로 분류합니다. X-ray 검사를 진행하여 골다공증으로 인한 압박 골절 등이 있는지 알 수 있습니다.
  2. Examples of the muscle relaxants include methanesulfonic acid pridinol, tubocaurine chloride, eferzone hydrochloride, tazanidine hydrochloride, chlorophenesin hydrochloride, tolverizone hydrochloride, dantrolene sodium, baclofen, and lamp ferrizone hydrochloride. do.
  3. 골절은 골다공증의 가장 흔하고 심각한 합병증입니다. 주로 척추와 고관절의 뼈가 부러집니다. 넘어질 때 땅에 팔을 짚으면서 손목의 뼈가 부러지는 경우도 많습니다. 
  4. ed amount of chlorine ions and an active ingredient, and a power supply having a polarity inversion means, a safe, efficient and continuous absorption can be achieved for a long time. Obtained. Furthermore, by optimizing the amount of chlorine ion and polarity inversion time added in the present device, the drug is not affected by the polarity of the drug, and the drug can be ad
  5. As the sedative agent, for example, chloropromazine hydrochloride, atropine sulfate, fluphenazine enenate and the like are used.

KR20010110754A - Iontophoresis device - Google Patent

7 is a cross-sectional view showing a specific configuration example of the iontophoresis device according to the present invention.Fig. 1 (b) shows a form in which a hydrophilic conductive layer containing chlorine ions is laminated separately under the electrode member. 100b illustrates a first electrode structure, and 110b illustrates a second electrode structure. The first electrode structure 100b includes a hydrophilic conductive layer 102b containing a predetermined amount of chlorine ions, a hydrophilic conductive layer 103b containing at least one active ingredient 104b, and silver and silver chloride. It consists of an electrode member 101b made of a mixture. The second electrode structure 110b includes a hydrophilic conductive layer 112b containing a predetermined amount of chlorine ions, a hydrophilic conductive layer 113b containing at least one active ingredient 114b, and a mixture containing silver and silver chloride. It consists of an electrode member 111b. In addition, a power supply device 120b having a polarity inversion means for changing the direction of the current between the first electrode structure 100b and the second electrode structure 110b includes an electrode member of each of the first electrode structure and the second electrode structure. It is electrically connected to 101b and 111b. In this embodiment, the redox reaction of the electrode and the chlorine ion is performed efficiently.

(PDF) Pharmacological treatment of osteoporosi

  1. 반면, 심평원은 70세 여성으로 1년 이상 골흡수억제제(본비바주)를 투여했으나 골밀도 검사상 T 스코어가 지속적으로 감소한 환자의 포스테오 청구건은 급여로 인정했다. 급여기준 상 환자 연령이..
  2. As anti-tuberculosis agents, for example, stratomycin sulfate, kanamycin sulfate, isoniazid, ethambutol hydrochloride, pyrazinamide, ethanebutol hydrochloride, pyrazinamide and the like are used.
  3. Polypeptides represented by the formula (wherein X1 represents D-Ser or D-Trp) or salts thereof (see US Patent No. 4086219, US 4124577 US Pat. No. 4393997, US Pat. No. 4317815).
  4. e hydrochloride, tripelena
  5. On the other hand, development has also been made with respect to electrode improvement for long time use, and Japanese Patent Laid-Open No. 9-276416 discloses an electrode having a main electrode made of an active electrode and a reproducing electrode made of an inactive electrode. In addition, Japanese Patent Laid-Open No. 4-312471 discloses a device that can be used for a long time by detachably replacing an electrolyte reservoir in a housing having an inactive electrode. However, in the device using these active electrodes, the regeneration or reuse of the electrode itself is disclosed, and the effect on the drug absorbency caused by the competing ions generated during the energization or the added electrolyte is not particularly considered. Can not.
  6. The present invention relates to a polarity inverted iontophoresis device capable of long-term dosing control on a transdermal or transmucosal membrane. More particularly, the present invention relates to an iontophoresis device that can maintain safety and stable absorbency for a long time efficiently by using an electric driving force and can be manufactured at low cost.

That is, the iontophoresis device according to the present invention comprises a first electrode structure and a second electrode structure each having an electrode member made of a hydrophilic conductive layer containing at least one active ingredient and an active electrode material, and a first electrode structure. And a power supply electrically connected between electrode members of the second electrode structure, the power supply having a polarity inversion means for changing the direction of current between the two electrode structures, wherein at least one of the first electrode structure and the second electrode structure is chlorine ion. It includes, and the amount of chlorine ion (Pmg) before administration is to satisfy the following formula (1).Examples of the circulatory solvent include alprostadil, limaprost, sodium azagrerel, chloropidogrel, veraprosto, cyprosten, iroprost, attaprost, clean frost, ethyl isosafentoate, ethyl hydrochloride, and mesylic acid. Hydroergotamine, pamicogrerel, tranilast, probucol, candesaltanylcexetyl, sodium citrate, DX-9065a, heparin, low molecular weight heparin, nifedipine, eonidipine hydrochloride, diltiazem hydrochloride, tranilast, etc. This is used.

골다공증 질환백과 의료정보 건강정보 서울아산병

In addition, the development of a device using a polarity inversion device is also advanced. In order to suppress the generation of harmful hydrogen ions or hydroxyl ions at an inactive electrode, Japanese Unexamined Patent Publication No. 60-34396 discloses a positive current energy amount and a negative value. The ratio of the amount of current energy is about 2: 1 to 7: 1. European Patent No. 076676 discloses adjusting pH by switching polarity from 0.0027 Hz to 10 Hz. In addition, Japanese Laid-Open Patent Publication No. 4-224770 discloses adjusting the pH by switching the positive and negative of the voltage applied between both electrodes. In these devices, the polarity is reversed during energization by using an inactive electrode which does not cause deterioration of the electrode itself, thereby improving skin irritation by suppressing pH change. However, the improvement of the generation of gas such as oxygen or hydrogen is not performed, and the gas is filled in the device for a long time, and therefore, a special structure such as a gas draining hole is required, and thus, it is difficult to manufacture the electrode assembled therewith. Was still not solved.Although the Example and comparative example of this invention are demonstrated in detail based on an experiment example below, this invention is not limited to these Examples. In Experimental Example 1, the influence of the electrode material on the electrical properties and the absorbency in the polarity inversion current was evaluated in vivo. Experimental Example 2 examined the absorbency and electrical properties in the rat of the electrode structure of the present invention. Experimental Example 3 examined the relationship between the amount of chlorine ions and the polarity inversion time in the basic drug. Experimental Example 4 examined the absorbency and electrical properties in the rat with respect to the relationship between the amount of chlorine ion and the polarity inversion time in the acidic drug. Experiment 5 carried out an absorption test in rabbits of fentanyl citrate using the electrode structure of the present invention.In addition, it is preferable in economical efficiency and manufacturability that the electrode member of the active electrode in the present invention is manufactured by conductive ink printing. The conductive ink is mainly composed of conductive particles, a binder, and a diluent, and the conductive particles of the present invention are not particularly limited as long as the conductive particles contain silver and silver chloride. Such conductive inks include commercially available inks containing silver, such asAs an antipyretic, analgesic, anti-inflammatory agent, for example, aspirin, sodium salicylate, sulfirin, indomethacin, diclofenac sodium, loxoprofen sodium, fervi, zaltoprofen, pyroxicam, nimesled, methoxycamp, cerek Seecove, thialamide, morphazone, buprenorphine, hydrogen bromide epsazosin, pentazocin, butyric acid tartaric acid, tramazole, ketrolac, meperidine hydrochloride, morphine hydrochloride, morphine sulfate, hydro Morphine, fentanyl citrate, fentanyl, mopezolac and the like are used.과도한 음주를 삼가고, 금연하며, 적절한 유산소 운동, 스트레칭, 제자리에서 뛰기 등의 운동을 하면서 골량을 유지해야 합니다. 짠 음식을 피해 염분과 함께 칼슘이 소실되는 것을 방지해야 합니다. 1주에 2회씩은 약 15분 정도 햇볕을 쬐어 뼈에 필요한 비타민 D를 충분히 합성시켜야 합니다. 카페인을 많이 먹으면 소변과 대변으로 칼슘이 많이 배설됩니다. 단백질 음식을 적당하게 섭취하는 것은 칼슘 흡수에 도움이 됩니다. 하지만 단백질 보충제나 동물성 단백질을 지나치게 많이 먹으면 칼슘 흡수율이 떨어집니다.

골다공증성 골절, 복용약 선택 주의해야 - 당신의 건강가이드 헬스조

As angiogenesis inhibitors, for example, angiogenesis inhibitor steroids (see Science Vol. 221, p. 719 (1983)), fumargiol derivatives (eg o-monochloroacetylcarbamoylfumagiol, o-dichloroacetyl Carbamoylfumagiol and the like (see European Patent Application No. 357061, 359036, 386667, 415294) and the like.EMBODIMENT OF THE INVENTION Below, this invention is demonstrated in detail, referring drawings as needed.On the other hand, the reaction efficiency of an electrode and chlorine ion changes with the mobility of chlorine ion in a hydrophilic conductive layer. In particular, in a hydrophilic conductive layer using a polymer base such as gel, the efficiency is extremely poor, and in order to compensate for this, the amount of chlorine ions needs to be increased. Furthermore, the drug absorbency varies depending on the mobility of ions of the same polarity as that of the drug. In other words, when the drug is anionic, the chlorine ion to be added substantially becomes a competitive ion with the drug. Therefore, the use in the range which has little influence on the absorbency of a drug is desired. Therefore, if the drug is a neutral or cationic material, a material having substantially different contention ions with the drug is selected, and the amount of chlorine ion contained in the hydrophilic conductive layer is not less than the amount represented by the following formula (1) required for the reaction. Ramen upper limit is not particularly limited.The electrode member is formed by printing a conductive ink containing at least silver and silver chloride. The composition ratio or mixing ratio of silver and silver chloride of the electrode member is preferably 1: 9 to 9: 1. The electrode member may further include a halogen compound.

wordhippo_NVUdesktop-dfp:600x338

Common forms of iontophoresis include a power supply, a pharmaceutical reservoir electrode, and an electrolyte reservoir electrode. The electrode includes an active electrode represented by silver or silver chloride and an inactive electrode such as carbon, platinum, and titanium. The inert electrode generates hydrogen ions and oxygen gas on the anode side and hydroxyl ions and hydrogen gas on the cathode side during energization. Hydrogen ions and hydroxyl ions produced by these inactive electrodes are known to cause skin irritation or to lower the drug yield.Further, US Patent No. 4406658 describes that iontophoresis is performed on both electrodes by one application by providing a means for switching the polarity of the electrodes in a device in which the polarities of the electrodes are reversible. In addition, Japanese Patent Laid-Open No. 9-503136 describes switching of polarity as a method for reducing stimulation during energization. However, the above conventional technology is not a polarity inverting device for the purpose of prolonged drug administration, and does not describe a device for obtaining a safe or stable absorption for a long time.FIG. 6 shows the concentration in fentanyl serum when the polarity inversion current was conducted for 8 hours using the electrode structure in Example 20. FIG. Serum concentrations of fentanyl lasted at about 10-15 ng / ml over a long period of time during energization. Moreover, the skin irritation of the device affixed part after the end of energization was not observed. From these results, it was confirmed that the polarity inversion type energization by the electrode structure according to the present invention can be administered continuously and safely for a long time.

Therefore, as a preferable form for avoiding these problems, an active electrode comprising two electrode structures containing a predetermined amount of chlorine ions and at least one active ingredient, and a mixture containing at least silver and silver chloride provided in each electrode structure And a power supply device electrically connected to the electrode member of each electrode structure and provided with a polarity inversion means for changing the direction of current between the two electrode structures. In this type of device, chlorine ions which correspond to the polarity inversion time in any electrode member even when anion extracted from the skin on the anode side and the silver ion of the electrode cause irreversible reaction or a subtle deviation in the polarity inversion time occurs. Since excess chlorine ion is contained as silver chloride more than reaction amount, and chlorine ion is contained in each electrode structure, it is not influenced even by long electricity supply.Specifically, when the first electrode structure has a polarity at the start of energization, when the first electrode structure is the anode side and the second electrode structure is the cathode side, chlorine ions contained in the first electrode structure react with the silver ions of the electrode on the anode side. On the cathode side, silver chloride of the electrode member is oxidized so that chlorine ions elute in the second electrode structure.(Where T is the polarity reversal time (minutes) before the polarity is reversed after energizing in a certain direction, and I is the average current (mA))

[헬스클리닉] 골다공증 척추골절 환자, 치료약 선택이 중요

건강-연변일보 Yanbian Dail

서울아산병원은 신뢰도 있는 건강정보 콘텐츠를 제공하여 더 건강한 사회 만들기에 도움이 되고자 합니다.콘텐츠 제공 문의하기As a result, an increase in the concentration of the compound in serum due to transdermal absorption of the compound occurs 30 minutes after administration, and a decrease in the concentration of the compound in serum occurs after the transdermal absorption is stopped for the next 90 minutes, and the electrode device unit 4 again returns. Transdermal absorption occurs at the positive electrode, concentration in the serum rises, and repetition of the pattern that returns to the original height, that is, when the electrode device unit 4 containing the compound becomes the positive electrode, transdermal absorption occurs. The concentration of the compound in the stable pulsed serum, in which serum concentration rises and transdermal absorption stops at a time less than that, and the concentration in serum decreases, is repeated over 24 hours.On the other hand, in Examples 12 to 14 and Comparative Examples 4 and 5, the influence of the polarity inversion time on the absorbency and electrical properties of fentanyl citrate was examined. This fell. In Comparative Example 5, in particular, a voltage increase was observed during energization, and the insulation state was obtained. On the other hand, in the range of polarity inversion time of Examples 9 to 14, the voltage increase tendency was observed during energization in Example 14, but no significant change was observed.[Wherein R1 'is Ser or Aib, R2' is Met or naturally occurring fat soluble amino acid, R3 'is Leu, Ser, Lys or aromatic amino acid, R4' is Gly or D-amino acid, R5 'is Lys or Leu, R6 'Is Met or a natural fat-soluble amino acid, R7' is Glu or basic amino acid, R8 'is Val or basic amino acid, R9' is Trp or 2- (1,3-dithioran-2-yl) Trp, R10 'is Arg or His, R11 'denotes Lys or His, R12' denotes Lys, Gln or Leu, R13 'denotes Phe or Phe-NH 2 ] or a salt thereof (Japanese Patent Laid-Open No. 5-32696, et al. 4-247034, EP 510662, EP 477885, EP 539491), peptide fragments at the N-terminus of humanized PTH (1 → 34) (hPTH (1 → 34)); (GW Tregear et al., Endocrinology, 93,1349-1353 (1973). P. 691 (197 8)] is used.If the active ingredient is neutral or cationic, a resin or polymer containing a chloride of the quaternary ammonium which does not form an ionic species competing with the drug (for example, the cationic component in these amines is substantially immobile) can be added. It is more preferable to add these at the anode on the anode side and the cathode side from the viewpoint of drug absorbency and conduction characteristics. 4 illustrates a case where each electrode structure has the same structure. In the case where the ionic species substantially competing with the movement of the drug during energization is immovable, a form as shown in FIG. 4 may be mentioned. In FIG. 4, 300 shows two electrode structures. The various electrode structures 300 are composed of at least one active ingredient 303, a hydrophilic conductive layer 302 containing a predetermined amount of chlorine ions, and an electrode member 301 made of a mixture containing silver and silver chloride. . In addition, a power supply device 310 provided with a polarity inversion means for changing the direction of current between the electrode structures 300 is electrically connected between each electrode member 301 of the first electrode structure and the second electrode structure. As an advantage of this form, it is possible to manufacture without distinguishing each electrode structure, and to eliminate the complexity. In other words, it is also advantageous in terms of efficiency and economics.

정형외과 Flashcards Quizle

In the device for administering iontophoresis produced in Example 24, the portion of the conductive medium in one of the two electrode device units 4 and 5 in pairs is described above. Both the compound and methylglucamine are replaced with a medium consisting of a gel in which a quarter amount is mixed, and a device for administering iontophoresis having different concentrations of compounding compounds in the positive electrode device unit is prepared.On the other hand, many diseases require long-term continuous drug administration, and invasive treatment such as drip is mainly performed in such patients. However, the treatment by drip etc. requires not only hospitalization but also a great burden on the patient. Sustained releases or embedded preparations are currently being investigated to address such shortcomings, but there are limitations in these formulations when strictly controlling blood levels. You will not be able to stop your medication if you have very heavy side effects. Iontoporesis is also noted as a new drug delivery system (drug delivery system) instead of an injectable drug that can respond as a continuous administration method for a drug requiring such precise dosage control. In other words, it is possible to absorb as much as an injection, and furthermore, if the drug is developed as a drug that can be self-administered by the patient, the path to home treatment is opened. In addition, it is possible to generate an arbitrary absorption pattern by precise control of the energization time, and in particular, it is considered that more effective drug treatment can be realized in a drug requiring dosage control.Wherein R 1c and R 3c represent hydrogen or an alkyl group having 1 to 6 carbon atoms, R 2c represents hydrogen or a D-α-amino acid, and R 4c represents hydrogen or an aliphatic acyl group which may be substituted with 1 to 8 carbon atoms. Oligopeptides and endorphins, such as peptides or salts thereof (see US Patent No. 4277394, European Patent Application Publication No. 31567), are used.'골다공'은 뼛속에 구멍이 많이 생긴다는 뜻이며, 골다공증은 뼈의 양이 줄어들어 뼈가 얇아지고 약해져 잘 부러지는 질환을 의미합니다. 사춘기에 성인 골량의 90%가 형성되고, 35세부터 골량이 서서히 줄어들다가 50세 전후에 폐경되면서 매우 빠른 속도로 골량이 줄어듭니다. 폐경 후 3~5년 동안 골밀도의 소실이 가장 빠르게 일어납니다. -예방 -치료 -운동 -약물: 골흡수억제제-Ca, vitamin D, estrogen, biphosphonate/ 골형성촉진제: androgen, steroid, fluoride, PTH. distal radius proximal femur spinal compression

골다공증 치료방법/칼슘이 풍부한 식품/칼슘 하루 권장량

Video: HEMATOLGO

Cymopoietin; Thymic fluid factor (THF): thymophilic factor (FTS) and derivatives thereof such as formula (VIII):In Example 26, after energizing for 30 minutes under the conditions of inversion, the conditions for stopping the energization for 10 minutes and then inverting the polarity to resume the energization were adopted, except that the rats were ions under the same conditions as in Example 26. Toporesis administration was performed to investigate the concentration of compounds in serum.

12 역학 Doing Data Science 역학 아꿈사 스터디 자

As the drug antagonist, for example, levartol tartarate, nalofine hydrochloride, protamine, naloxone and the like are used.Here, the active ingredient is anionic, and the polarity inversion by the power supply device is regularly repeated.

The redox reaction at the electrode surface on the anode side at each inversion time of the present invention is preferably designed to mainly react with chlorine ions in the hydrophilic conductive layer.As the hormonal agent, for example, β-estradiol, enanthate testosterone, prednisolone succinate, sodium dexamethasone phosphate, methiazole and the like are used.② 비타민 D 결핍 비타민 D는 장에서 칼슘의 섭취를 증가시키고 신장에서 칼슘의 배출을 감소시켜 체내 칼슘을 보존하는 작용을 합니다. 또한 뼈 분해를 막아서 골다공증을 예방하는 효과가 있습니다. 나이가 들면 피부, 간, 신장에서 만들어지는 활성 비타민 D가 감소합니다. 이는 비타민 D의 섭취와 일광 노출이 충분하지 않은 경우에도 부족해집니다.  상호작용. Bisphosphonate. 계 골흡수억제제. 파미드론산디나트륨 등. 를 병용투여시 혈청 칼슘농도가 급속하 Examples of the antiulcer agent include ornoprostill, cimetidine, pamotidine, linititidine hydrochloride, metoclopramide, omeprazole, lansofurazole and the like.

Table 2 shows the results obtained in the above Examples and Comparative Examples. In the case of using the electrode material of Example 1, an instantaneous voltage increase during polarity switching during energization and a tendency of voltage increase gradually during energization were observed. This change in electrical characteristics is considered to be due to the gradual lack of chlorine ions (present as silver chloride) in the electrode when energizing as the cathode side in the first electrode structure. In Example 2, the voltage change during energization was not recognized. On the other hand, in Comparative Example 1 in which the inactive electrode was used, after the voltage suddenly increased during energization, it became insulated and could not conduct electricity. Thus, in Comparative Example 1, it is considered that the gel contact area changes due to gas generation during energization. The total absorption amount of lidocaine was remarkably low at about 1.8 mg in the comparative example, while the total absorption of lidocaine was about 3.2 to 3.4 mg in Examples 1 and 2.As the anti-tuberculosis agent, for example, streptomycin sulfate, kanamycin sulfate, isoniazid, ethambutol hydrochloride, pyrazinamide and the like are used.Progesterone-releasing hormone (LH-RH), derivatives having the same action as LH-RH, such as the following formula (1):As antihyperlipidemic agents, for example, pravastatin sodium, mysticstatin, fluvastatin sodium, cerivastatin, atorstatin and the like are used.These physiologically active peptides may be of human type or derived from other animals such as cows, pigs, chickens, salmon, eel, and moreover, chimeric bodies derived from humans and their animals. Furthermore, the active derivative may be a part of the structure is changed. For example, pig-derived insrin, or calstonin from pigs, chickens, salmon, eel, or chimeric bodies of humans and salmon (IX):

EO

⑧ 우울증 우울증을 앓는 여성은 뼈의 손실 속도가 빨라집니다. 원인은 확실하지 않습니다.As the cardiac agent, for example, transbioxocampo, deopilol, dopamine hydrochloride, dobutamine hydrochloride, ubide carrenone and the like are used.FIG. 6 is a graph showing the concentration in fentanyl serum when the polarity reverse type energization is carried out in Example 20. FIG.

1 (a) and 1 (b) each show a structural example of the iontophoresis device according to the present invention.The hydrophilic conductive layer of each of the electrode structures contains a predetermined amount of chlorine ions (wherein the predetermined amount refers to the amount of chlorine ions included in advance before the current is supplied) and is energized by a polarity inverting power supply device. This predetermined amount of chlorine ions is calculated from Faraday's law. In general, the number of moles (M) of a material that is moved by electricity is represented by the following current (I), application time (T), number of charges (Z), and constant (F) of the material.In the serum when iontophoresis was administered to rats under the same conditions as in Example 21, except that the device for iontophoresis administration as used in Example 21 was used and the time interval between inversions was 15 minutes. The compound concentration was investigated.

Wherein Xd represents L- or D-Ala, Yd and Zd represent Gly or D-amino acids having 3 to 9 carbon atoms, respectively, or salts thereof (see US Patent No. 4229438); and other thymic hormones [ See footsteps of medicine, Vol. 125, No. 10, pp. 835 to 843 (1983), such as thymosin α1 and β4, cymic factor X, and the like.

Priority Applications (3)

Preparation of (S) -4- (4-guanidinebenzoylamino) acetyl-3- [3- (4-guanidinebenzoylamino)] propyl-2-oxopiperadine-1-acetic acid dihydrochloride 단, 골흡수억제제 중 데노수맙을 사용한 후에 순차적으로 테. 단, 골흡수억제제. 를 투여할 때 일반적으로 치료 첫해 골밀도 저하가 가장 많

8

③ 폐경 에스트로겐은 골밀도를 유지해 줍니다. 폐경으로 에스트로겐이 감소되어 골다공증이 생길 수 있습니다.⑥ 가족력 어머니나 자매가 골다공증일 경우 골다공증이 발병할 확률이 높습니다.The electrode structure includes an organic amine as a pH adjusting material. Specifically, the pH adjusting substance is at least one of meglumine, tromethol, triethanolamine and aminoacrylate, for example. In addition, the power supply device may have a means for shorting a circuit and / or a means for providing a non-energization time for a predetermined time when performing polarity inversion. The polarity inversion by the power supply device is at least one or more times, and the polarity inversion time of one time is preferably 1 minute to 2 hours. As the current applied by the power supply device, at least one of direct current, pulse direct current, and pulse depolarization direct current is used.

Family Applications (1)

  1. ④ 약물 항응고제(헤파린), 항경련제, 갑상선호르몬, 부신피질호르몬, 이뇨제 등의 치료제는 골다공증을 일으킬 수 있습니다.
  2. 골다공증의 치료법은 골 형성을 증가시키거나 골 소실을 방지하여 현재의 골량을 유지하는 것입니다. 비타민 D 합성을 위해 규칙적으로 운동하고 자주 일광욕을 해야 합니다. 식사 시 뼈를 튼튼히 하는 칼슘이 풍부하도록 신경 써야 합니다. 음식을 짜게 먹으면 나트륨이 소변으로 빠져나갈 때 칼슘도 함께 배출되기 때문에 저염으로 식사해야 합니다. 음주, 흡연, 카페인, 인스턴트 식품, 패스트푸드, 탄산음료, 흰 설탕 등의 가공식품 섭취를 피합니다. 
  3. Examples of antifungal agents include anpoterisin B, itraconazole, fluconazole, myconazole, 2-[(1R, 2R) -2- (2,4-difluorophenyl-2-hydroxy-1-methyl-3- (1H). -1,2,4-triazol-1-yl) propyl] -4- [4-2,2,3,3-tetrafluoropropoxy) phenyl] -3 (2H, 4H) -1,2, 4-triazolone and the like are used.
  4. ..해열, 진통, 소염제, 항류마티, 이완제, 진해거담제, 항궤양제, 진정제, 항전간제, 항우울제, 항알레르기제, 당뇨병치료제, 항결핵제, 호르몬제, 마약길항제, 골흡수억제제, 혈관신생저해제..
  5. As the vasodilator, for example, oxyphedrine hydrochloride, tolazoline hydrochloride, phosphamethane sulfate, nicardipine hydrochloride, verapamil hydrochloride, sapa paverine and the like are used.

Eluent: 0.05 mol phosphate buffer (pH 3.5) / acetonitrile / 0.5 mol sodium 1-octavesicpibate = 85/15/1Examples of the antihypertensive agents include hydralazine hydrochloride, budralazine, prazosin hydrochloride, mesylic acid doxazosin, cartolol hydrochloride, clonidine hydrochloride, maleic acid enalapril, captopril, drapril, hydrochloride hydrochloride, manadipine hydrochloride, pinassidyl, Minoxidil, losaltan, candesaltan cilexetil, valsartan, termisantan, irubesaltan and the like are used.

Examples of the bone resorption inhibitor include (sulfur-containing alkyl) aminomethylene bisphosphonic acid, raloxifene, sodium arendronate, disodium cadmium dibasic, tiblon, simandronate, lizdronate, chlordronate disodium, pare Calcitriol, calcitriol, alpha calcitriol, didronel sodium, ifriflavone, minodronic acid and the like are used. 포스테오주(테리파라타이드) 개최/시행일: 2016-12-01, 관련 근거: 고시 제 2016-223 호(약제) 가. 투여대상 기존 골흡수억제제(alendronate, risedronate, etidronate 등).. The present invention comprises two electrode structures (first electrode structure and second electrode structure) comprising an active electrode made of a mixture containing silver and silver chloride having the following constitution and a predetermined amount of chlorine ions and at least one active ingredient. By using the power supply device with the polarity and the polarity inversion means, the chlorine ion is set to the amount according to the polarity inversion time in order to suppress the migration of the contention ion, so that the drug does not affect the polarity of the drug, It is also a device that can be administered percutaneously with good reproducibility over a long period of continuous absorption. The method of constructing the device and reinforcing the patch, that is, the composition and structure of the backing is not particularly limited.또한 골절의 위험이 높아집니다. 심할 경우 허리를 구부리거나 기침을 하는 등 일상생활 중에도 뼈가 쉽게 부러질 수 있습니다. 50~70세 여성의 골절은 주로 손목에서 먼저 발생하는 경우가 많습니다. 70대 환자들의 경우 고관절 및 척추의 골절이 흔하게 발생합니다.

12 역학

The composition ratio or mixing ratio of silver and silver chloride of the electrode member is preferably 1: 9 to 9: 1, more preferably 1: 5 to 5: 1 particularly preferably 1: 2 to 2: 1 do. Further, a halogen compound, such as a water-soluble or insoluble polymer and resin such as quaternary ammonium chloride, such as ethyl acrylate, methyl methacrylate, trimethyl ammonium chloride copolymer, cholestyramine, etc., is added to the electrode member. The electrode reaction becomes more efficient.As the arrhythmia treatment agent, for example, propuranolol hydrochloride, oxyprenol hydrochloride, procainamide hydrochloride, lidocaine, phenytoin, tartaric acid metoprolol, verapamil hydrochloride, diltiazem hydrochloride and the like are used.On the other hand, if the drug is an anionic substance, since the chlorine ion eluted from the electrode or the added chlorine ion becomes a substantially contention ion, a range in which the effect is small, that is, a predetermined amount of chlorine ion is 500 times or less of the amount required for the reaction, especially It is preferable that it is 1 to 100 times. Therefore, the amount of chlorine ions is represented by the following formula (2).Iontophoresis is a transdermal absorption promotion system that uses electricity as an external stimulus. The principle is that molecules that occupy positive electric field generated between the anode and the cathode by energization come out of the anode, and the negatively occupied molecules It is to promote the permeation of the skin barrier of chemical molecules based on the force from the cathode to the anode (Journal of Controlled Release, Vol. 18, 1992, pp. 213 to 220: Advance Drug Advanced Drug Delivery Review, Vol. 9, 1992, p. 119: Pharmaceutical Research, Vol. 3, pp. 318-326, 1986).2 is a diagram showing a configuration example of a power supply apparatus used in the present device. As shown in the drawing, the power supply device 200 includes a power supply (battery) 201, a boosted power supply 202, an output adjustment circuit 203, an output inversion circuit 204, a microcomputer 205, and the like. Here, the output inversion circuit 204 is provided with a switch means for switching polarity, and the microcomputer 205 is provided with a timer means for controlling the polarity inversion time. At the time of switching, it is also possible to provide depolarization due to a short circuit or a non-energization time for a predetermined time, thereby inverting the polarity.

As a result, 30 minutes after administration, the compound concentration in serum decreases due to transdermal absorption of the compound, and when the electrode device unit 4 becomes the anode again, transdermal absorption occurs and the concentration in the serum is repeated. That is, when the electrode device unit 4 containing the compound is composed of a positive electrode, transdermal absorption occurs, the serum concentration increases, and at other times, the transdermal absorption stops and the concentration in the serum decreases. It is pointed out that the peak value of the pulse of the heavy compound concentration increases slightly with each iteration.10-week old male SD rats (body weight about 400 g) were used for drug administration. After the rat was anesthetized with pentobarbital, the abdomen was shaved and a device for iontophoresis was attached to the site. Further, two electrode terminals made up of the pair of devices are connected to a timer-equipped switch 3, as well as to a current generator 2 (50 kHz, 50% duty) and a power source 1 as shown in FIG. Switching iontophoresis administration was performed for 24 hours on the conditions which became the permeation | transmission current (current density 0.075 mA / cm <2> : total current 0.72 mA). In addition, the site | part through which an electric current flows is the site | part which the hydrophilic porous thin film contacted with skin, and the area was 9.62 cm <2> . At this time, the switching condition is the reversal of the polarity of the electrode every 5 minutes. The current flows in one direction at the time interval set by the timer, and then the relay is operated at the moment to reverse the polarity and resume the energization. It was done. After the start of administration, blood was collected over time, and the concentration of compound in serum was measured by HPLC. ⑤ 골흡수억제제(비스포스포네이트) : 골밀도를 증가시키고 골절률을 낮춥니다. 낮은 흡수율, 잦은 위장 장애, 골수 억제 효과 등을 최소화한 여러 약제가 개발되고 있습니다. ⑥ 불화나트륨(NaF) : 골량을..

As a method of selectively inhibiting the movement of chlorine ions in the hydrophilic conductive layer described in the above (c), for example, by using an anionic polymer in the hydrophilic conductive layer, a device for suppressing the movement by electrical repulsion may be mentioned. have. Such anionic polymers include, for example, polyacrylic acid, sodium polyacrylate, methoxyethylene maleic anhydride copolymer, methoxyethylene maleic acid copolymer, isobutylene maleic anhydride copolymer, isobutylene maleic acid copolymer, carboxyvinyl polymer, Acidic synthetic polymers, such as a cation exchange resin which added the sulfone group as a functional group, Polysaccharites, such as arginic acid, sodium arginate, carboxy cellulose, and carboxymethyl cellulose, and proteins, such as gelatin, These are single or two. Used in combination of more than one kind. In addition, the efficiency is further improved by using the device structure described in FIG. 1B.The chlorine ion can be added to each electrode structure in various forms. For example, electrolytes, pH adjusters, buffers, skin protectors, irritants, stabilizers, thickeners, wetting agents, surfactants, solubilizers, dissolution aids, humectants, absorption accelerators, pressure-sensitive adhesives, tackifiers, preservatives, etc. You may add the function to an additive. For example, an anion exchange resin or polymer in which potassium chloride, sodium chloride, calcium chloride, glucosamine hydrochloride, triethanolamine hydrochloride, hydrochloric acid, and quaternary ammonium groups are added as functional groups, such as cholestyramine, arginine hydrochloride, methyl acrylate, methyl methacrylate, When using methacrylic acid trimethylammonium ethyl copolymer etc., the chlorine ion which has the said function is contained. In addition, when such an additive is used, a substance (competition ion species) having the same charge as a drug which is a counter ion of chlorine ion must be used within a range that does not affect the absorbency of the drug. Therefore, as a more preferable method of supplying chlorine ions, for example, hydrochloric acid, hydrochloride of an active ingredient, a substance in which chlorine ions are added to a substantially floating polymer, irrespective of the presence or absence of energization, or a hydrochloride thereof, and a suitable combination of foreign substances It can also be used.③ 칼시토닌 : 골다공증에 사용하면 통증이 감소하는 효과가 있습니다. 칼시토닌은 환자가 장기간 움직이지 못하거나 내과 질환으로 골 손실이 발생한 경우, 골다공증을 유발하는 약제를 투여받은 경우에 골 손실을 예방하고 치료하는 데 효과가 있습니다.As a result of intensive studies to achieve the above object, the present inventors have found that a predetermined amount of chlorine ions is contained in two electrode structures (first electrode structure and second electrode structure) having an electrode member made of a mixture containing silver and silver chloride. The present invention has been found by containing an active ingredient and supplying electricity to a power supply device having a polarity reversing means. Furthermore, as a result of intensive research, the device is not influenced by the polarity of the drug, and the amount of chlorine ion according to the polarity inversion time for suppressing the migration of the competitive ion is set so that the drug is highly reproducible with high bioavailability. The present invention has been found by discovering that it can be administered transdermally. In the present invention, a material for supplying the amount of chlorine ions and chlorine ions of the electrode structure having an active electrode in order to safely conduct long-time electricity supply by the energization method using the polarity reverse means without causing a decrease in absorption efficiency, furthermore Initiate the best device. As a result, it is possible to control the dosage accurately for a long time, and to obtain a safety and inexpensive polarity inversion type iontophoresis device.Examples of local anesthetics include lidocaine hydrochloride, tetracaine hydrochloride, procaine hydrochloride, benzocaine hydrochloride, ethidocaine hydrochloride, prilocaic hydrochloride, dibucaine hydrochloride, bubivaca hydrochloride, cocaine hydrochloride, ethyl aminobenzoate hydrochloride, orthocaine hydrochloride. , Oxetazaline hydrochloride, mepivacaine hydrochloride and the like are used.

The hydrophilic conductive layer of each electrode structure may be a matrix structure in which the active ingredient is dispersed, or a laminated structure having a drug holding layer to apply a high concentration of the active ingredient to the skin contact surface, but the distribution state of the active ingredient is particularly limited. It doesn't work. In addition, the laminated structure is particularly useful when the active ingredient is chemically unstable, or a drug or an expensive drug which exhibits a strong pharmacological effect in a small amount, and the holding means containing the active ingredient is used in contact with the hydrophilic conductive layer immediately before use. do. In addition, the hydrophilic conductive layer is not particularly limited in gel, solution type and the like.Next, using a fentanyl citrate as a basic drug, an electrode structure was prepared according to the formulation shown in Example 20, and the long-term sustained absorbency in polarity reverse conduction by the absorption test in rabbits was confirmed. The electrode is a PET-formed sheet containing a conductive ink containing silver and silver chloride (molar ratio of silver to silver chloride of about 1: 1) and then molded into a cup shape (PET, inner diameter 24mm, effective area 4.5cm 2 ) 0.7 g of the formulation of the formulation shown in each Example and the comparison was filled. In this experiment, Japanese white male male rabbits (about 3.0-4.0 kg in weight, skin-washed with hair clippers and electric razors were degreased using cotton wool containing 70% ethanol aqueous solution). Two electrode structures (the first electrode structure and the second electrode structure) are attached to each other, and energization is performed using a pulse depolarization direct current current (frequency 50 kHz, duty 50%) by a short-circuit switch, so that the constant current is 0.1 mA / cm 2 . It was energized with a polarity inversion time of 30 minutes and a total energization time of 8 hours, blood was collected from the ear vein over time, and the concentration of drug in serum was measured by GC-MS method.Carried out using the iontophoresis device for the same as used in Example 24, and a set of a current density up to 120 minutes from the start of administration, and the current density to 0.1mA / cm 2, then is used to 0.05mA / cm 2 Except for the above, iontophoresis was administered to rats under the same conditions as in Example 24, and the concentration of compound in serum was examined.As another comparison object, an electrode device unit having the same composition as in Example 21 was used as the electrode device unit for the positive electrode, except that the electrode was made of silver foil, and a commercially available printed silver / silver chloride electrode was used as the electrode device unit for the cathode. Comparison with the concentration of compounds in serum when iontophoresis administration in one direction without changing the polarity (except the electrode unit for the negative electrode is changed every hour; current density of 0.075 mA / cm 2 ) In contrast, the serum concentration in the steady state obtained in Examples 21 and 22 had a skin permeation promoting effect of more than expected at about 80% thereof. In general, once the polarity is reversed, the compound once migrated to the skin side receives the opposite iontophoresis effect (the effect of the drug moving toward the cathode), thereby obtaining the expected skin penetration promotion by the iontophoresis. Although it was feared that this could not be done, it can be said that this result was obtained by the selection of a suitable compound, the inversion time of the polarity and the suitable composition in the electrode device unit.In addition, the amount of chlorine ions (P: mg, molecular weight 35.5) corresponding to the number of moles required for the redox reaction at the electrode is represented by the average current (In: mA) and the polarity inversion time (Tn: min) according to the polarity inversion interval. Here, when the polarity inversion time and the average current value are set at random during the polarity inversion energization, the maximum required amount per one polarity inversion during the energization period is selected.

When diclofenac sodium is used in the drug, the chlorine ion (quaternary ammonium chloride) added in Examples 7 and 8 is a competing component, but the amount of the quaternary ammonium chloride added is small, and the polarity inversion time is short. Equivalent to 3 (about 30% of the dose). However, in Comparative Example 3, due to the silver ions eluted from the anode side during energization, skin coloring in contact with both device structures after the energization was confirmed.Using the device for administration, after energizing for 30 minutes as reversal conditions, the current was stopped for 10 minutes, after which the polarity was reversed to resume energization, and the current density was set to 0.05 mA / cm 2 again. At the start of administration, the rats were subjected to iontophoresis under the same conditions as in Example 21 except that the electrode device unit 4 was the anode, and the concentration of the compound in the serum was examined.⑤ 운동 부족 어릴 때부터 활발히 뛰어노는 아이들이 나중에 골밀도가 높습니다. 체중을 싣는 운동, 점프, 깡총 뛰기 등이 뼈의 건강에 도움이 됩니다.However, when the active electrode is used, there is a problem of competition with the cationic agent due to a pair of ionic species with chlorine ion on the anode side, and a decrease in absorption due to competition with an anionic drug due to chlorine ions eluted from the electrode on the cathode side. There was a problem. In addition, since the electrode itself is oxidized or reduced, it is difficult to maintain its performance as an active electrode when used for a long time.

In the device for administering iontophoresis produced in Example 24, the portion of the conductive medium in one of the two electrode device units 4 and 5 in pairs is described above. A device for iontophoresis administration in which the compound was mixed with only the other electrode device unit 4 was replaced with a medium consisting of a gel containing no compound and methylglucamine. Using the device for administration, after energizing for 30 minutes under the conditions of inversion, the conditions for stopping the energization for 30 minutes and then inverting the polarity to resume energization were adopted, and the current density was set to 0.05 mA / cm 2 again. At the start of the administration, iontophoresis was administered to rats under the same conditions as in Example 21 except that the electrode device unit 4 was the anode, and the concentration of compound in serum was examined.The time course of the compound concentration in serum in Examples 21 and 22 is shown in Fig. 8 (in Fig. 8, the black circle indicates the result of Example 21 and the white circle indicates the result of Example 22). In any of the administrations, the compound concentration in serum reached about 2000 ng / ml after 2 hours, after which the concentration was maintained for 24 hours. That is, it was found that the conduction is maintained for a long time by switching, and the high transdermal absorption in response to the conduction is maintained for a long time. In addition, as a comparison target, the energization in one direction was performed without the inversion of the electrodes using the iontophoresis administration device of Example 21. As a result, the voltage suddenly increased after about 1.5 hours, and thereafter, the energization was poor.On the other hand, if the active ingredient is anionic, the added chlorine ion becomes a bonded ion species having substantially the same charge as the drug. A method for minimizing the effects on the drug absorbency caused by such competitive ion species, (a) adding chlorine ions in a range not affected by the drug absorbency, (b) setting the polarity inversion time shorter than usual (C) selectively inhibiting the movement of chlorine ions in the hydrophilic conductive layer, (d) not adding chlorine ions to the hydrophilic conductive layer in the cathode structure at the first polarity, and the like. These may be used in combination.

(Asahi Kagaku Genkyusho Co., Ltd., etc.) are mentioned, It is used disperse | distributing silver chloride powder to them. Commercially available inks containing silver chloride, such as JEF-314, JEF-321 series, DW 2275, DB 92342, DB 92343 (above, Nippon Archson) or the like may be used in combination with or alone with silver inks. Furthermore, graphite ink, a diluent, etc. are added and used as needed. Since graphite ink can reduce the content of expensive silver, it is preferable to mix and use it with the ink containing silver and silver chloride. Further, additives for increasing the reaction efficiency of the electrode, for example, surfactants, ion exchange resins, water-soluble substances and the like can be added. These conductive inks are printed on a backing film or the like constituting the electrode structure, and examples of such printing methods include screen printing. The printed electrode shapes include, for example, sheet printing, mesh printing, multilayer printing, and multilayer printing in which an active electrode is printed on an inert electrode such as carbon, or these may be pattern printed in various forms.5 shows another configuration example of the iontophoresis device according to the present invention.The electrode structure has an insulating support having a pit formed therein, and the electrode member and the hydrophilic conductive layer are accommodated in the pit of the insulating support, and the surface thereof is semi-permeable membrane, selective permeable membrane, control membrane, or hydrophilic porous thin film. It can be configured to cover.

① 칼슘 제제 : 적절한 칼슘은 골량을 유지해 주며 골량의 소실을 지연합니다.In addition, the serum sample is diluted with physiological saline solution, then applied to a pretreatment column (130nd Elut C18), adsorbed to the column, and eluted with methanol solution containing 1% TFA. The solvent was evaporated under and then dissolved in HPLC eluent and applied to HPLC. The conditions of HPLC are as follows.The hydrophilic conductivity layer may be a member having various porous or capillary structures permeable to the drug (hereinafter, simply referred to as a porous body), or a combination thereof. Such porous bodies include organic porous bodies such as natural fibers such as cellulose, semisynthetic fibers such as cellulose acetate and nitrocellulose, fiber aggregates formed from polyethylene, polypropylene, nylon, polyester and synthetic fibers chemically modified thereof, and the like. Sheet, cloth such as woven fabric or nonwoven fabric, porous polypropylene, porous polystyrene, porous polymethacrylate, porous synthetic resin such as porous nylon, porous polysulfone, porous fluororesin and the like.

After the polarity inversion, on the anode side, silver chloride precipitated on the electrode surface is oxidized in the first electrode reaction so that chlorine ions elute in the first electrode structure. On the cathode side, chlorine ions eluted into the second electrode structure in the first electrode reaction react with the silver ions of the electrode member.Examples of antitussive expectorants include ephedrine hydrochloride, codeine phosphate, picoperidamine hydrochloride, amproxol hydrochloride, bromoxy hydrochloride, salbutamol sulfate, tulobuterol hydrochloride, formoterol fumarate, azelastine hydrochloride and ketotifen hydrochloride , Picoperidamine and the like are used.As a result, the concentration of the compound in the serum is increased by transdermal absorption of the compound 30 minutes after administration, and then the transdermal absorption is stopped or transdermal for 50 minutes until the electrode device unit 4 becomes the anode. The decrease in the absorption rate causes a decrease in the degree of increase in the concentration of the compound in the serum. When the electrode device unit 4 is made of the anode again, the percutaneous absorption becomes higher and the concentration in the serum rises to its original height. Repetition, that is, the concentration in the serum of the compound is maintained within a certain range through the 24 hours of the administration period.

Thus, the number of moles (P) of chlorine ions used in the reaction at each inversion time is represented by the following equation.As antidepressants, for example, amino tryptiline hydrochloride, imimipramine hydrochloride, chloromipramine hydrochloride, desipramine hydrochloride, maprotiline hydrochloride, phenelzin sulfate and the like are used.By setting the polarity inversion time described in the above (b) to be shorter than usual, for example, from 1 minute to 30 minutes, the total amount of chlorine ions added can be reduced.Here, the active ingredient is a polar or inverted periodically by the power supply as a neutral or cation is repeated regularly.As the hemostatic agent, epinephrine, menadione sodium bisulfite, acetomenaftone, tranexamic acid and the like are used.

As a diuretic agent, for example, acetazolamide, metazolamide, chlorothiazide, furosemide, triamterene, amylolide, aminomethorozin and the like are used.On the other hand, in the active electrode, oxidation or reduction occurs at a voltage lower than that of water electrolysis. As a representative electrode material, silver or silver chloride electrodes are known. Usually, silver electrodes are used on the anode side, and the electrolyte reservoir further contains counter substances (for example, chlorine ions, etc.) necessary for the redox reaction with the electrodes. That is, metal ions (eg, silver ions) eluted from the anode side electrode react with the combustion ions in the reservoir to produce insoluble precipitates (eg, silver chloride). As a result, the movement of the metal ions to the skin is substantially suppressed, so that the active electrode has higher safety for the skin than the inactive electrode.뼈의 특성상 초기에는 특별한 증상이 나타나지 않습니다. 초기 증상 중 하나는 척추뼈가 약해져서 척추가 후만 변형되거나 압박되어 신장이 줄어드는 것입니다. 심한 경우 척추가 체중을 지탱하지 못해서 외상이 없더라도 척추의 앞부분이 일그러지게 됩니다. 

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