TW320562B - - Google Patents

Description

320562 A7 _B7 Fifth, the description of the invention (1) The scope of pharmacology, medicine and medicinal chemistry of the present invention _ and provide for patients who have been marinated with flustine, fenlafaxine, minacipran or duloxetine "Methods and Sister Compounds for Adding Serotonin, N-Adrenaline and Dopamine Utilization Ο In the past 20 years or more, research in pharmacology has focused specifically on neurons containing monoamines in humans. Physiological phenomenon. It has been continuously discovered in this category and has been shown in serotonin, spleen, dopamine, and dopamine, and various receptors function and control or influence processes that can regulate many body organs and functions. In particular, menstrual serotonin is an important factor for many physiological and psychological functions. Probably, the most significant discovery made in the chemistry of the metabolites in recent years is dysstatin, an inhibitor of serotonin reuptake, which is an extremely effective medicine for treating depression. Because it is an inhibitor of resorption, it can eliminate the effect of the low serotonin absorption carrier to absorb serotonin. M increases the utilization rate of serotonin at the synaptic site. The functional disorder of serotonin neurons caused by excessive absorption can cause depression and other diseases of the central nervous system. Complexion is not only particularly effective in suppressing noise, it is also very effective in treating many other diseases. Printed by the Staff Consumer Cooperative of the Central Department of Economic Affairs of the Ministry of Economic Affairs (please read the precautions on the back before filling in this page) A new generation of propagule is duloxetine * which is an inhibitor of serotonin and norepinephrine reabsorption . It is currently an advanced clinical trial drug in the treatment of depression and urinary incontinence. It is also very effective. Venlafaxine and Minasset are also inhibitors of serotonin and norepinephrine reuptake. Although the initial role of flutein is to inhibit the reabsorption of serotonin, the staircase action of the monoamine in the brain connects serotonin with serotonin and dopamine. Therefore, the increase in the utilization rate of serotonin is also due to Zhengxian -4- This paper standard is used in China's national #quasi (CNS) 84 specifications (210X297 mm) A7 B7 5. Description of the invention (2) Epinephrine and dopamine Utilization of fenlafaxine and minaset for M also increases the use of dopamine. The present invention provides a better comparison of the utilization of amines of nalcitram and duloxetine. An increase in the use of linuolu (alprenolol), sickle (spiperone), pintoto R (penbutolol), and tertatolol, the first choice of doxorubicin and dopamine utilization rate. In an intermittent manner, the absorption of serotonin and norepinephrine was inhibited by dulostatin M and M. It is the method of increasing the use of serotonin, fenlafaxine, and rice to increase serotonin, norepinephrine, and dopa. Increase the utilization rate of the above three * Use M to do it. Add serotonin in cyanototin, fenlafaxine, and minaxite to the serotonin, the normal method, including combining the first type of ingredients with the 100% (WAY 100135), SPYBO »( Pindolol), (S) -UH-301, sugar cloth suspected propranolol (Proranolol), S and other compounds of the following formula were selected and used together OH I Ar-0-CH2CHCH2NHZ \ _ j 1 1 V Ri (please Read the precautions on the back first and then fill out this I) r > Pack. Ordered by the Ministry of Economic Affairs Central Bureau of Precision Industry Beigong Consumer Cooperative Printed by Ar Department

‘Paper scale is applicable to China National Standard (CNS) Α4 specifications (210X297mm) A7 B7 V. Description of invention (3: Printed by the Employee Consumer Cooperative of the Central Bureau of Economic Affairs of the Ministry of Economic Affairs R3

Ra

R2.

R2 ·

R2 · R2 '

R2 ·

Or R2 · (please read the note Ϋ on the back before filling in this page). Binding · Order This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297mm) 320562 A7 B7 V. Invention description (4)

! U is a methyl group that may be substituted on one of the three connected carbon atoms as required; 1 to 2 are hydrogen, Ci- "alkyl, trifluoromethyl, and hydroxyl (Ci-CU alkyl) -〇- , (Ca- "alkyl) -S (0)» »-or halogen, 1? 3 is (: 3-(:« »cycloalkyl or bis-alkyl group with the following formula, (please read the back Matters needing attention before filling this page) G-

The printed bags of the Employees Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs where a and C are independent 1-5, b is 0-5, and (a + c) is greater than 2; Z is a straight bond or a branch of "-(; 1〇 Alkanes, alkenes or alkynyl groups, (C4-Ce alkynyl) optionally substituted with (Μ4 alkyl or phenyl, a bicyclic alkyl group of the following formula, G-

This paper scale is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) A7 B7 Printed by the Employee Consumer Cooperative of the Central Bureau of Economic Affairs of the Ministry of Economy V. Description of invention (5) The case can also be C2-C10 alkanes substituted by phenyl Group, the phenyl group of which may be substituted as previously defined • or (Ci- “Subalkyl ^ -T-iCi-C ^ alkyl). Where T is -0-, -S-, -so- or- s〇2-; where each G is an independent Kj or Ci-CU subalkyl group; X is -H, -COY, -CH or dagger * alkyl; Y is -OH, -O-iCi- C * alkyl) or -NHz; R · and R ·. Are cerebrum «or G-Cs alkyl or the carbon atom to which they are attached to form a ring of C3-Ce cycloalkane; P is 0, 1, Or 2; A is -0-, -S-, -NH- or -KCHS-; and it is 0, 1, 2, or 3, or one of its kind that is acceptable on the B plant. The present invention also includes the first category The ingredients are synergistic with the second category of the name of the above-mentioned medicine. It is even available for the treatment of diseases caused by the low utilization of serotonin, polytryptamine or norepinephrine, including the need for administration The patients under treatment include the first type of ingredients and the above names An adjunct treatment of a second type of compound. The present invention also provides a method of using the above-mentioned lotion combination that can enhance the action of the first type of compound and the method of using the above-mentioned sister to manufacture a drug for the same purpose. In addition, it provides a treatment Diseases caused by low utilization of serotonin, norepinephrine, or dopamine and methods for manufacturing aspirants. Furthermore, the present invention provides a better way to complete the above-mentioned adjuvant therapy, of which the second category The application of the ingredients can provide a stable amount in the blood -8- The standard of this paper is the Chinese National Standard (CNS) Α4 specification (210Χ297 mm) (please read the precautions on the back before filling this page)

V " suit ·

, 1T A7 B7 Printed by the Beigong Consumer Cooperative of the Central Bureau of Economic Affairs of the Ministry of Economic Affairs 5. Description of the invention (6), this amount is sufficient to provide a substantially stable effect of the first type of ingredients, and also provides changes to complete the invention The composition of the preferred mode. In this article, all temperatures are in degrees Celsius, and all ratios of * · quantities and degrees are expressed in K weight units unless otherwise specified. The commercially available fluorochrome, N-methyl-3- (p-trifluoromethylphenoxy) -3-phenylpropylamine, is in the form of hydrogen chloride and is a racemic mixture of its two mirror isomers. US Patent 4,314,081 is an early reference for this compound. Robertson et al. * In J. Med. Che .. 31. 1412 (1988) taught us the method of separating the R and S mirror isomers of calastatin and pointed out that their activities as serotonin absorption inhibitors Similar * The term "flusetine" in this article will use M to denote any acid addition M or tourmaline age and also includes racemic mixtures or R or S dysprosium isomers. Durostatin · Η-methyl-3- (1-lylyloxy) _3- (2-thiazolyl) propylamine is usually a hydrogenated hydrogen chloride ((+) mirror isomer type. USA専 利 4,956,38 8 First of all, let me know its high efficiency. "Durosertine" in this article means any acid addition brew or the molecule's engraving_. Venlafaxine is often seen in the literature and in US Patent 4,761,501 I was also taught about its synthesis and its activity as an inhibitor of the absorption of serotonin and epinephrine. In this patent, venlafaxine was named compound A. U.S. Patent 4,478,836 teaches me Minasep Ν, Ν-diethyl-2-aminomethyl-phenylphenylpropanecarboxamide) and is designated as the preparation of Example 4. The patent describes its compound as an antidepressant cocoon. Moret et al. * 1¾ Mje.iLT_Q.PhajaacolQKy ZL ·, 1211-19 (1985) describes its lapping activity. -9- This paper scale is applicable to China National Standard (CNS) A4 specification (210X297 mm) (please read the note on the back first Fill in this item X) f Install.

11T A7 B7 Printed by the Employee Consumer Cooperative of the Central Bureau of Samples of the Ministry of Economic Affairs 5. Description of the invention (7) Known that duloxetine, flutatin K and other first-class ingredients can be added with 5-hydroxytryptamine (5-HT) and dopamine (DA) Utilization rate of Eugenic S Adrenaline (HE) * and the second component drug enhances this precious property. The second type of ingredients, which have common characteristics, can be used as antagonists of serotonin 1A receptors. (S) -UH-301 ((S) -5-fluoro-8-hydroxy-2-dipropylamino-tetrahydronaphthalene) is widely known by pharmacologists and chemists. Hillver et al., In M ^ jj ^ Che ·, ............ 13-, 1541-44 (1990), taught me the synthesis method and Moreau et al., In Brain Res. Bull. 29. 901 -04 (1992) ¾ Provides many intramedullary materials with the compound. 8 ^ 11 < ^ 1 ^ 〇1 et al. Disclosed in U.S. Patent 3,466,325 Kebrinolu (1- (1-methylethyl) amino-3- [2- (2-propenyl) -stupid Oxy] -2-propanase), and instruct it as the preparation of Example 5. VAY 100135 (N- (Third-Butyl) -3- [4- (2-Methoxyphenyl) pyrrol-1-yl] -2-phenyltrisamine)》 Abou-Gharbia et al., United States, 4,988,814 Zhonghe », which also pointed out that the compound has 5-HT1Ag affinity. Cliffe et al. · # · K Kfid. Che .. 3ft. 1509-10 (1993) indicated that the compound was an antagonist of 5-HTα. Spirobole (8- [4- (4-fluorophenyl) -4-oxobutyl]-: 1-benzyl-1,3,8-triazole [4,5] dec-4-one ) Is a widely known compound, which can be seen in U.S. 3,155,669 and 3,155,670. Its activity as an antagonist of 5-HT1A's can be tested by Middleiiss et al., Neurosci. And B-LiLb. £ -hay -._ Rev. 1 fi r 75-82 (1992) ° Tataduo K (8- (3-Third-Butylamino-2-Hydroxypropoxy) -Dibenzodihydroperazine was fed by Ma len et al., US 3, 960, 891, -10- This paper size is applicable to China National Standard (CNS) A4 specification (210X297mm) tl. (Please read the notes on the back before filling in this page) f Pack. Ordered knowledge · 32056? A7 B7 Printed by the Employee Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economy V. Inventions Explain (8) and inform us that it can be used as a beta-epinephrine receptor. Its other activities include the 5-HT1A antagonist activity here, and it has been issued since its original patent. Propland Nuo® (1-isopropylamino-3-U-naphthyloxy) -2-propanase via 0〇 »1;» ^ 1 * et al. * In the United States_Patent 3,337,628 is shown to be similar to dotaxol霣 之 beta-blocking surface. In addition, other sex 霣 is also well known to pharmacologists. «Butuo 霣 (1- (third-butylamino> 2-hydroxy-3- ( 2-cyclopentyl-phenoxy) propane) by Ruschig et al. • Yumei専 利 4,551,493 tells me and describes it as beta-learning sole. Its (-) Xing (+) dysprosium isomers are beneficial, (-) dysprosium isomers are for the purpose of the present invention It is better, but in this article, both of the "isomers" and racemic mixtures are included in the "Yuanbu Tuo K" "Fan Fan." Pin Duo (4- (2-hydroxy-3- Isopropylaminopropyloxy) -indole) was described by Troxler et al. In U.S. Patent 3,471,515 and described this compound as a beta-blocker. This compound is usually administered as a beta-mixture but some people will Two kinds of yin-shaped mixtures are divided and if the single isomer product is used in the set "use case", the mirror-shaped isomer of (-) is better. In this article, "Pindolu" includes two Y-shaped isomers and racemic mixtures. The compound of formula I is known by Beedle et al., Published in U.S. Patent 5,013,761, and its description is listed in K for reference. The synthesis and properties of this compound include 5H T, a Antagonist activities are listed in this patent. Particularly preferred compounds of formula I include, for example, the following compounds. People should understand that the following compounds are only typical of the compounds of formula I, but this kind of compound package -11- This paper scale uses the Chinese National Standard (CNS) A4 specifications (210X297mm) ^ (Please read the precautions on the back before filling this page ) Outfit

, TT Ministry of Economic Affairs, Central Bureau of Precinct Employee Consumer Cooperative Printed A7 B7 V. Description of invention (9) Including the number of faces, as mentioned earlier, the types of beauty and beauty in the ben. I should further understand that * Although the following alternatives and dysprosium isomers are particularly beneficial in some cases, other salts, mirror isomers, Li isomers and racemic mixtures are still very popular The compound of formula I is also used as the drug m of the present invention. 1- (4-Indenyloxy) -3-cyclohexylamino-2-propanase • Mubutenedioic acid salt; Yan_-1- (4- «| indolyloxy) -3- (4 -Phenyloxyhexyl-amino) -2-propanase, oxalic acid >>; indolyloxy) -3- (2-phenylethylamino) -2-propanase, oxalate; 1- (4- Indolyloxy) -3- (3-phenylethylamino) -2-propanase, oxalate; 1- (4-oxolyloxy) -3- (4-phenylethyl Amino) -2-propanase • oxalic acid m; 1- (4-indenyloxy) -3-cyclopentylamino-2-propane_, butadiene acid hydride; 1- (4-β 丨Indolyloxy) -3- 瑁 heptylamino-2-propane_; (S)-(-)-l- (4-indolyloxy) -3-cyclohexylamino-2-propanase , Oxobutenedioic acid M; (0-1- (4-0¾ indolyloxy) -3-oxoheptylamino-2-propanase · oxobutenedioate; 1- (4-indole Yloxy) -3- (3-methylcyclohexylamino) -2-propanase; 1- (4-indolyloxy) -3- (4-methylxenylamino) -2- Propanol; (Please read the precautions on the back before filling this page)

、 1T Κ -12- This paper scale is suitable for China National Standard (CNS) Α4 specification (210X297mm) A7 B7 Printed by the Consumer Cooperative of Central Central Bureau of Economics of the Ministry of Economy V. Description of invention (10) 1- (4-Ind Indolyloxy) -3- (5-phenylpentylamino) -2-propanase, oxalate; 1- (4-indenyloxy) -3- (6-phenylhexylamino) -2-Propylase, oxalic acid SR; 1- (4-Indoxybenzyloxy) -3- (2,3-dimethylhexyl-amino) -2-propanase, monoacid_; (+ ) -1- (4-lumenolyloxy) -3- (3-pentylamino) -2-propanase; (R >-( +) -l- (4-lumenolyloxy 3 -Cyclohexylamino-2-propanase, succinate; indoyloxy) -3-cyclohexylamino-2-propanase, succinic acid M; 1- (2-trifluoromethyl-4 -Benzimidazolyl) -3- (4-phenylbutylamino) -2-propanyl;; (outer) -1- (4-indenyloxy) -3- (n-conylamino) -2 -Propanol; (internal) -1- (4-indolyloxy) -3- (n-subsylamino) -2-propanase; 1- (1-lesyloxy) -3-cycloheptan Aminoamino-2-propanase, oxalate; 1- (2-cyclopentylphenoxy) -3-cycloheptylamino-2 ~ propane, oxalate; 1- (2- 瓖 Hexyl Oxy) -3-oxooctylamino-2-propane , Oxalate; 1- (2-cycloheptylphenoxy) -3- (1,2,3-trimethyl-2-propylamino) -2-propanol, oxalate; and 1- (2-Cyclopropylbenzyloxy) -3- (1,1-dimethylbutyl-amino) -2-propanase, oxalic acid》 ° Wain compounds of formula I where the Ar group is based or The substituted indole groups constitute a better family of 5-HT1A antagonists, and the compound of formula I, the -13- paper size of the Chinese National Standard (CNS) A4 specification (210X297 mm) (please read (Notes on the back then fill out this page)

* tT -h £ * A7 B7 printed by Beigong Consumer Cooperative of Central Central Bureau of Economic Affairs of the Ministry of Economy V. Description of Invention (11) Z is (c4-c89 alkyl) and may be substituted with g-Ca alkyl or phenyl as appropriate The 'or Z' represents a C2-C10 alkyl group optionally substituted by phenyl, and a phenyl group may optionally be substituted by MR2, which further constitutes a particularly good class of compounds that can be used in the present invention. All of the above-mentioned compounds used in the present invention and those of the present invention are listed in this document for reference. Although all the first-class and second-class compounds are very useful and valuable *, some combinations are particularly valuable and better. Here are the following: flusetin / pindol》 duloxetine / pin Dodecetine / Partebutirol Duloxetine / Partebutor Flutsetin / Tirop "Noruduloxetine / Tirotti" Norfluxetine / Dotaduroduro Satin / tatadoroflustine / 4- (2-hydroxy-3-cyclohexylaminopropoxy)-«! Indodurostatin / 4- (2-hydroxy-3-cyclohexylamino) Propoxy) -Indodo usually uses flusetin or dulostatin as the first component and the best treatment method. Skilled readers will understand that all compounds used in the present invention can form SK and usually use its》 as a medicine, because it is often easier to form crystals and purify than You Hickard. In all cases, the use of the above-mentioned salts as edible substances is covered in the description of this article and is generally preferred, and all compounds of yi yi shang -14- This paper scale is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm ) (Please read the precautions on the back before filling out this page).

'1T Α7 Β7 Printed by the Employee Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economy V. Description of the invention (12) Acceptable salts are included in its name. The final analysis of the medicine used in the present invention must be based on the expensive knowledge of the use of the medicine according to the nature of the medicine_health bed test and the characteristics of the patient and other diseases including the patients treated by the physique. set up. Here also a general description of the dose and certain better amounts will be provided. First of all, we will give guidance on the amount of certain medicines separately, and K will create any necessary guidance for the sisters, so that everyone can take this instruction K to administer each component of the medicine. Flusetine: from about 1 to about 80 mg once / day * M is preferably from about 10 to about 40 mg once / day, preferably from about 20 to about 80 mg once for the treatment of eating disorder and obsessive-compulsive disorder / Day; Durostatin: from about 1 to about 30 mg once / day, K is preferably from about 5 to about 20 mg once / day; Venlafaxine: from about 10 to about 150 mg 1 to 3 times / Day, Κ is from 25 to about 125 «g three times / day; Minasep M: from about 10 to about 100 mg 1 to 2 times / day, M from about 25 to about 50« g twice per day Good; Pinduo: from about 1 to about 60 g 1 to 3 times / day, M from about 5 to about 60 mg 1 to 3 times / day, preferably from about 1 to about 10 times g / Day Yi Jia 9 鸰 Butuoluo: from about 2 to about 80 mg once per day, preferably from about 10 to about 80 mg once per day, preferably from about 2 to about 20 Erke once per day; "Proplano": from about 10 to about 240 mg 1 to 2 times / day, preferably from about 10 to about 120 mg twice / day, preferably from about 40 to about 240 mg 1 to 2 times / day; -15- The size of this paper is in accordance with China National Standard (CNS) Α4 specification (210Χ297mm) (please read the notes on the back before filling This page) • Γ equipment _

'ST Α7 Β7 Printed by the Consumer Labor Cooperative of the Central Bureau of Economic Development of the Ministry of Economy V. Description of the invention (B) 4- (2-hydroxy-3-cyclohexylaminopropoxy) indole: from about 1 to about 50 μm 1 to 2 times per day, K is preferably from about 1 to about 10 mg twice per day. Using more commonly used language, we can select the amount of the first type of ingredients and select the second type of ingredients according to the spirit of the above guidelines and set the range from about 1 to about 250 mg / dose. A kind of sister-in-law. Depending on the compound, the preferred amount may be from about 1 to about 100 mg / facet, and it may even be found that the preferred dosage range is from about 1 to about 50 mg / dose, and from about 1 to about 25 mg / dose. ideal. The adjuvant therapy of the present invention is "administration of the first type of component and one of the second type of component M in any manner provides two compounds in the body in the same amount at the same time. All kang compounds are available in a palatable version, and they are also used for normal application. Therefore, it is better for the auxiliary sister compound K to swell. It can be applied together in a single-sided form or separately. However, oral administration is not the only way, or even the only better way. For example, it may be more necessary for people who are forgetful or hate oral medicine. One of these drugs can be administered in one way, such as oral K, while the other can be administered transdermally, transdermally, intra-statically, intramuscularly, intranasally, or intrarectally. * Depending on the particular circumstance. The route of administration can be any method, depending on the physical properties of the drug, the convenience of the patient, and the convenience of the patient's caregiver. However, the best one for the sister-in-law combination is the application of a single tortoise compound. Therefore, the combination of a first-type component and a second-type component is a significant specific embodiment of the present invention. . Such a composition may be any medically acceptable physical form, but K is an orally acceptable pharmaceutical composition. This kind of auxiliary rib medicine composition contains an effective amount of each compound, the effective amount of -16 — This paper standard is used in China National Standards (CNS) A4 specifications (210X297 mm) (please read the note on the back $ Item and then fill out this page) f Packing and ordering 320562 A7 _B7 printed by the Beigong Consumer Cooperative of the Central Bureau of Economics of the Ministry of Economy V. Description of the invention (in) and the daily dosage of the compound to be marinated is W. The most unit of each supplementary agent may contain the daily amount of the compound described, or it may contain a portion of one day, such as a third dose. In addition, each dose of M unit may contain the total dose of one compound and the amount of another compound. In this case, the patient will use one sister unit for each day and one or more units containing only another compound. The amount of each _ contained in each ul unit depends on the sex K and other factors of the drug used for treatment, such as instructions for the _ help treatment given. Looking at the second category of component compounds * as the same category, it has a short internal effect and accordingly only provides short-lived activity after each sole *. For example, Pintolu was routinely applied twice per day in the previous usage, and even more frequently. Therefore, when the second-type component compound is administered within the scope of the present invention, K can practically maintain a stable amount of the second type component in the patient's blood and be high enough to provide a way to enhance the stability of the actual effect of the first type component. Better. Of course * Neither the present invention nor any method of treating patients is intended to provide truly high blood levels and enhancement levels. Biological margins are usually different and can prevent accurate results from being stabilized. The term "substantially disagreeable" in this article means that the content of the blood will be strong enough to be stable enough to provide continuous improvement efficiency in comparison with the efficiency of the first component compound alone within a treatment day . Another way in which Kaulu actually substantiates the enhancement is by comparing the utilization of serotonin, norepinephrine and dopamine in the patient's brain. The term “substantially stable” means that the difference between the highest and lowest utilization rates on a treatment day does not differ to the power of 10. Another way to test the "stabilization in quality" is 1. 5 -17- the difference between the highest and lowest points is less than 10. 5-17- This paper scale uses the Chinese National Standard Rate (CNS) Α4 specification (210X297 mm) (Please read the precautions on the back before filling out this page) Γ A7 _B7 Printed by the Employees ’Consumer Cooperative of the Central Department of Economics of the Ministry of Economic Affairs A. _B7 5. Description of the invention (15) The power or the gap range is about 10 to 1.5 to about 3 . Such a method of applying the second ingredient can be performed by a method well-known to metalogist K. For example, the total daily mule amount of the second ingredient can be formulated to provide a way for the patient to achieve stable compound flow. Only test when there are many products • At least the following reference materials teach the insults of cable-bearing preparations: Germany 3635201, capsules; Naussie "Lee 634990, Zhandi; Germany Zheli 3237945, buccal film; sickle_Xinli 2732335 , Zhanmian; American special 52 60 0 66, cold glue; European special notice 361894, lipid «; Japan special 84-66710, wear leather stickers Η. «Pharmacists are familiar with the regulation technique K to adjust the sustained release formulations. M provides the necessary application rate of a given compound and can be used here as a second type of compound when preparing the formulation. Technology. The formulations of such second type component compounds can be combined with the selected first type component compounds to form a blue-and-white type. For example, the formulation can be combined into small lozenges or granules that provide a stable utilization rate of the compound of the second component, and the compound of the first component, such as a capsule. In addition, a transdermal patch can be prepared that has a relatively rapid release of the first-type component and a relatively slow-release area of the second-type component. Moreover, it is possible to prepare particles of the first type of components in the form of regular purification while particles of the second type of components are coated with a to provide a continuous release suspension. In this way, the utilization rate of the second-type component can be adjusted to provide the substantially stable amount of blood required in the blood * and thus the definite enhancement of the first-type component. Therefore, the sister compound that provides the first class of components with a strong stability-enhancing effect after changing κ is the preferred sister compound of the present invention. Except for the presence of the first-class components and the second-class components compounds * The auxiliary paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297mm) (please read the note Ϋ on the back before filling this page) Binding. Order Α7 Β7 Printed and printed by the Employee Consumer Cooperative of the Central Bureau of Economics of the Ministry of Economic Affairs. 5. The description of the invention (1 €) for the inert ingredients and formulations of the B compound are all by Fu Zheng. The formulation methods used in general medicine can also be used here. All general forms of sister compounds can be used, including noodles, chewable noodles 01, capsules, solutions, parenteral solutions, intranasal Kuanger or powder, tablets, suppositories, transdermal patches and suspensions . Generally, depending on the desired dosage and the type of composition used, the sister compound contains the compound from about 0.5% to about 50%. However, the amount of the compound should preferably be expressed, that is, the amount of each compound required to provide to patients in need of such treatment. Because the activity of the auxiliary sister compound is not the characteristics of the sister compound, the choice of the sister compound and the formulation is only convenient and economical. Any sister can be blended into the necessary form of any sister compound. After discussing the different sister compounds, we will show some typical formulations. When preparing capsules, the compound is mixed with diluent and the equivalent amount of the mixture is filled into the capsules. Common dilutions include inert powdered materials such as starches, powdered cellulose, especially crystalline and microcrystalline cellulose, sugars, sugars, sugar cane, granulated flour and the like. Edible powder. The bleaching agent is made by direct compression, wet granulation or dry granulation. The K-regulated substance usually incorporates the diluted surface, combined with W, slipped and decomposed, and the compound. Typical diluents include, for example, uninterrupted types of starch, lactose, cantina, kaolin, calcium phosphate or calcium sulfate, non-branched salts such as sodium carbamide and silt. Powdered vitamin derivatives can also be used. Typical combinations of agents are substances such as starch and gelatin and analogues such as lactose, fructose, and glucose. Natural and synthetic gums are also very convenient, including gum arabic, citric acid, methyl thyroxine, polyvinylpyrrolidine and the like. Polyethylene Glycerine, B-19- This paper uses the National Standards (CNS) A4 specifications (210X297mm) (please read the $ item on the back and then fill in this page) Pack ·,? Τ- h A7 B7 printed by the Consumer Cooperative of the Central Bureau of Samples of the Ministry of Economic Affairs V. Description of the invention (1?) The base fiber pheasant can also be used as a binding agent. In the lozenge compound, it is necessary to stick the thin M surface and the printer to the chess set. The slip agent is made from slippery talc, magnesium stearate and calcium, stearic acid and hydrogenated vegetable oil. Lozenge disintegrants are those that will swell and break the lozenge and release the compound when wet. It includes starch, clay, cellulose, alginate and gum. More special ones can even use corn starch, starch, methyl cellulose, agar, silicic acid β, wood cellulose, powdered natural sponge Yang Diaozi exchange resin, thin acid, yellow paradox, citrus pulp and carboxyl Methyl cellulose and sodium dodecanoate. The intestinal formulation Μ is usually used to protect the active ingredients from the strong acids. We thinly coat a polymer film that is insoluble in an acidic environment and soluble in a sickle ring in a solid type M to make such formulations. Typical couplers are ethyl phthalate cellulose, polyethylene glycol dicarboxylate, hydroxypropyl methylcellulose phthalate and ethyl hydroxypropyl methyl succinate . It is better to convert duloxetine and duloxetine-containing sister compounds into intestinal compositions, and even to formulate them into intestinal granules. A preferred intestinal composition of dulostatin includes a) —a core made of excipients acceptable by dulostatin and b) —an optionally separated layer c) Ethyl succinate hydroxypropyl methylcellulose < HPMC AS) and a medically acceptable "Drug Intestine" d)-a pill formulation with a supporting layer added as appropriate. The following examples show the preparation of such better formulations (please read the item on the back of $ before filling in this page).

, 1T Κ4 -20- This paper scale is applicable to the Chinese National Standard (CNS) Α4 specification (210Χ297 mm) A7 B7 V. Description of invention (1 is now printed by the Central Bureau of Standards of the Ministry of Economic Affairs Zhengong Consumer Cooperative Society 10 mg duloxetine Matrix / capsule material ―Yazhi― Granular sucrose-superior starch, 20-25 mesh 60.28 mg duloxetine duloxetine 11.21 hydroxypropyl methylcellulose 3.74 isolated hydroxypropyl methylcellulose 2.51 Sucrose 5.00 talc, 500 mesh 10.03 Intestinal tract HPHCAS, LF FU, Sh in-Etsu Chemical 25.05 Co., Tokyo, Japan Triethyl citrate benzylate 5.00 talc * 500 纗 目 7. 52 Retouching hydroxypropyl methyl Paclofen 8.44 Dioxide Peptide 2.81 Lu Shaoyou 141. 60 mg Suspension of duloxetine in 4% w / w hydroxypropyl methyl sulfone 21- (please read the note Ϋ on the back before filling in this Page) r The standard size of the paper used in the Chinese National Standard (CNS) A4 (210X2S »7 public daughter) Printed A7 B7 by the Employee Consumer Cooperative of the Central Escalation Bureau of the Ministry of Economy V. Description of the invention (19) Vitamin solution and KMS -12 CoBall Research Machine Fryia Hashinen AG, Rheinf el den (Nauze) studied the suspension surface to make the Durostatin calendar. I used a fluid bed dryer K with a Vurs ter column of 1 kg per batch to make this product. The separation calendar is formed by adding Μ of a 4% w / w solution of hydroxypropyl methylcellulose in water, in which sucrose is also dissolved, to form a separation calendar. The suspension coated for the production of glazes * I will cool the pure water To 101 and add polysorbate, triethyl lemon «acid and silicon emulsifier and disperse or dissolve. Then add HPMC AS and talc and stir until homogenized, and add nitrogen oxidation》 M and completely neutralize HP MC AS, until The polymer solution is complete. Add 0.5% w / w carboxymethylcellulose aqueous solution to this suspension and mix it thoroughly. Maintain the intestinal suspension at 20 υ during the coating process. Then maintain the inlet temperature At 50 υ, and add the intestinal suspension Ml 5 «L / min spray * rate to the partially completed pellets in the Wurst er column. When the intestinal》 float is completely added * M50t in Wurster : Dry Can products, then place M 601C on the tray in the dry room for 3 hours Then add 45% weight / weight ft of hydroxypropyl methylcellulose solution containing titanium dioxide and malonan as the shaping cocoon. The pellets are completely dried in the flow dryer and filled. Put into size 3 gelatin capsules. The blooming agent is usually coated with flavoring and used as a sealant or coated with a preservative M that forms a film to modify the solubility of the blooming agent. The compound can also be conjugated into a cocoon. It is as well-established today as it is * by adding a large amount of substances with good flavors such as glucomannan to the formulation. At present, it is also often used to dissolve the formulations similar to ingots to make the consumer _ type of patients at ease and avoid -22- This paper uses the Chinese National Standard (CNS) Α4 specifications (210X297 mm) (please first (Please read the precautions on the back of the feed and then fill out this page) · (-installation. Order 320562 A7 B7 V. Description of the invention (2 °) Avoid troubles that may disturb some patients _ solid "things difficult. When you need to use sister compound to do For the suppository, a general base can be used. Cocoa butter is a general-purpose suppository base, which can be modified by adding scorpions to slightly increase its viscosity. Water-soluble suppository bases include, in particular, the widely used difference The molecular weight of polyethylene is drunk. Recently, it is more and more popular to wear a leather patch. It typically includes a soluble resin or a partially dissolved drug in the resin compound, which is borrowed from a film Skinny contact. There are many patents in this category recently. Some people are also using other more complex stickers Η sister compound, especially he has a lot of holes and can take drugs through osmotic pressure through this clear _. Provide the following typical formulations for medical scientists to do data and satisfy curiosity 0 g Item 1 Use the following ingredients Μ to prepare hard gelatin pouches: (please read the notes on the back before filling in this page) η pack. 、 1Τ The Ministry of Economic Affairs Central Bureau of Accreditation Employee Consumer Cooperatives printed an amount of f gram / g pouch ) Flusertin, racemic mixture, gasified Ganoderma lucidum 20 mg m more than 30 starch 9 dried vine 200 m wax m magnesium 1SL grade set 260 * g-23- This paper scale is used by the Chinese National Standard (CNS) Α4 specification (210X297mm) V. Description of the invention (21) Α7 Β7 mm mm Preparation of lozenge flustine, racemic mixture (-)-Zhubuto using the following ingredients κ 溗 维素, microcrystalline silicon dioxide * Total fuming stearic acid "Hydrogenated hydrogen M ft (mg / g capsule) 10 40 400 10 __5 465 mg of mixed ingredients and compressed K to form a weight of 46 5 5 grams of velvet face < prepare the following ingredients Air-soluble _ Ingredients: (+) -Durostatin, Hydrogenated Plaque Product Exposed Ethanol Propulsion 22 10 10 25.75 (Please read the precautions on the back before filling this page)

I. Printed by the Ministry of Economic Affairs, Central Bureau of Industry and Commerce, Beigong Consumer Cooperatives (difluoromonocyanomethane) 70.00 Total M 115.75 Mix the active ingredients with ethyl acetate and add this compound to a portion of propellant 22, cool to- 30 t: And transferred to the filling device. Then put the required amount into a non-discriminatory steel container and dilute with K_propellant. Then connect the control valve to this container. -24- This paper scale uses the Chinese National Standard (CNS) A4 specification (210X297 mm) 320562 A7 ___B7 V. Description of invention (22) 钃 配 物 4 Prepare the following tablets containing 80 mg of active ingredient per β_: (+) -Durostatin, gaseous hydrogen M 20 mg (-)-«Butuo 60 mg powder 45 mg cellulose 35 mg polyvinylpyrrolidone (10% aqueous solution) 4 mg carboxymethyl Starch sodium Η 4.5 mg magnesium stearate 0.5 mg talc 1 g total ft 170 mg (please read the precautions on the back before filling this page) Printed by the Ministry of Economic Affairs, Central Bureau of Precinct Employee Consumer Cooperatives will be effective ingredients (starch Mix with Fibre Soybeans> Tongyun No. 45 mesh and completely mix the solution. The solution containing polyethylene-pyrrolidine noodles is mixed with the resulting powder, and then the mixture is passed through the American leptoma of the βl No. 4 mesh. Granules Κ 50 t; dry, and pass the No. 18 program of the US _ sieve period. Add the carboxymethyl fiber Sona, magnesium stearate, and talc added to the US sieve of the No. 60 program. The granules, after mixing, are pressed on the ingot machine to produce 170 mg of each seal賰 g..g .. hug ...... 5 .. Prepare the following capsules each containing 130 «g of active ingredient: flustine, racemic mixture, hydrogen chloride 30 mol Propranol® 100 mg starch 59mg-25- This paper scale is suitable for China National Standard (CNS) A4 specification (210X297mm), 11-line A7 B7 microcrystalline cellulose magnesium stearate, followed by m-dimensional Sumei lanthanum. Description of the invention (B) 59 mg of 2MJS 250 gram starch magnesium stearate and active ingredients, Tongbian No. 45 period and M 250 «g are filled into hard gelatin capsules. The BR BR fi is prepared as follows each containing 45 mg Suppositories of active ingredients _ = (+) -durostatin, hydrogen chloride salt 5 mg tirotino II no 40 gram saturated fatty acid glycerol alcohol 000 mg total amount 2,045 mg makes the active ingredient pass the beauty garden screening of «No. 60 program And suspended in the fatty acid glyceride which has been melted from the minimum heating. The mixture is then poured into a suppository of nominal 2 g volume and allowed to cool. The preparation is as follows. Every 5 «Lenghuan contains 70« g effective Suspension of ingredients (please read the notes on the back before filling in Page), ιτ, Ministry of Economic Affairs, Central Bureau of Standardization, Employee Consumer Cooperative Printed Flustine • Racemic Mixture Propranol S Carboxymethylcellulose Nano Syrup Benzoic Acid Solution Flavor Color Gasified Hydrogen Salt 10mg 60mg 50¾g 1. 25 «l 0. 10ml set the most quantitative -26 ^ The paper size is easy to use China National Standards (CNS) Α4 specifications (210X297 mm) Printed Α7 Β7 by the Ministry of Economic Affairs Employee Consumer Cooperative of the Central Bureau of Economic Development 5. Invention Instructions (24) Add pure water to an amount of 5 ml to make the active ingredient of the US-Taiwan sieves of the No. 45 stage of the US, and mix carboxymethyl cellulose and syrup to form a smooth ointment. Dilute the benzoic acid solution and the pigment with one portion of water and add to it • Stir. Add enough water to the required volume. Bintang Compound 8 can be prepared as follows: Intravenous injection formulations: (〇-durostatin • vaporized hydrogen salt 10 mg protripranol 21 20 mg isotonic "1,000 ml of liquid as mentioned above, the benefits of the present invention are in The first type of ingredients have the ability to increase the utilization of serotonin, norepinephrine and dopamine, which enhances the activity when treating the following different diseases. The increase in the utilization of serotonin is particularly important, and it is a better aspect of the present invention. Moreover, the present invention provides a faster onset of action than fluoxetine or duloxetine alone. The following experimental data clearly show the rapid onset of action M and the enhancement of monoamine utilization. The diseases treated by the adjuvant treatment method B of the present invention include depression, obsessive-compulsive disorder and obesity. In addition, the combination including duloxetine is preferred but it can also be a combination of fenlafaxine and minazetiran A more specific disease is urinary incontinence. Recently, many differences in the suppression of the disease have been clearer to the general public than before, and today, it is recognized as an extremely damaging disease and is one of the diseases affecting a large number of people . Suicide is the most restrictive The irritated sensation • But millions of people are not affected by such a stab * but live in part or completely in vain and also affect their families because of their suffering. Flustine's introduction is to treat depression It is a breakthrough of the disease and it is now easier to diagnose and treat than just ten years ago. -27- This paper scale is suitable for China National Standardization (CNS) Α4 specification (210 X 297 public) (Please read the precautions on the back first (Fill in this page), ΤΓMinistry of Economic Affairs Central Standards Bureau Employee Consumer Cooperatives printed A7 B7 V. Description of invention (deteriorated) Yu patients. At present, duloxetine is in clinical trials for the treatment of constipation and may also be listed as a detriment. Symptoms are usually caused by other diseases or diseases. For example, it is associated with Parkinson's disease, HIV, Ozheimer's disease, and anabolic ferment. Depression also has May be confused with any substance abuse or injury caused by public health, mental barriers or strokes, or sister-in-law behavior. All kinds of different anxiety disorders are auxiliary treatment methods of the present invention. The better compound of the compound. Obsessive-compulsive disorder This kind of patient is usually accompanied by a compulsory performance of non-essential and ceremonial behavior. Thoughts, orders, and similarity actions that transcend rational or reasonable attention are external special withdrawals for this disease. The affected patients may not be able to do anything other than the ritual held by patients with this disease. The United States and other B families are allowed to use flutidine to treat obsessive-compulsive disorder and it is effective. Obesity is a common disease in American people. It has been found that flusetin can cause K fat patients to lose weight and thus contribute to the patient's circulatory system and heart condition M and general well-being and vitality. Urinary incontinence is usually classified as stress or forced incontinence, but it depends on its root cause Whether it is due to the controlled disability of the sphincter or the excessive activity of the bladder muscles. Duloxetine can immediately control these two types of incontinence, so for many people who suffer from this comfort and disability Very important. In the present invention, M can be used to treat many other diseases, disorders, and diseases K and the following. In many cases, the classification of the diseases mentioned in this article can be found in the Interanal Disease Classification, the ninth edition (International Classification of I 2 8 _ This paper again uses the Chinese National Standards (CNS) A4 specifications (210X297 mm) (Please read the precautions on the back before filling out this page) Line A7 B7 Printed by the Central Consumers ’Bureau of the Ministry of Economic Affairs Employee Consumer Cooperative V. Invention Instructions (26) Diseases, 9th Edition 1ICD)) or American Psychotherapy Association (DSM ) Published Diagnostic and Statistical Manual of Mental Disorders 0 In view of this situation, for the sake of convenience, ICD or DSM numbers are also listed below. Depression, ICD 296.2 & 296.3, DSM 296, 294.80, 293.81, 293.82, 293.83, 310.10, 318.00, 317.00 Overseas Chinese headache pain, especially neuralgia food disorders, ICD 307.51, DSM 307.51 Premenstrual syndrome or post yellow «Phase syndrome, DSM 307.90 Alcoholism, ICD 305.0, DSM 305.00 & 303.90 Tobacco abuse, ICD 305.1, DSH 305.10 & 292.00 Panic disorder, ICD 300.01, DSM 300.01 & 300.21 Ignorance, ICD 300.02. DSM 300.00 Post-traumatic syndrome, DSM 309.89 Memory loss, DSM 294.00 Alzheimer's disease, ICD 290 Social phobia * ICD 300.23, DSM 300.23 Hyperactive attention deficit disorder, ICD 314.0 «Crazy, ICD 312 Balance disease, ICD 312, DSM 312.39 & 312.34 Marginal personality abnormalities, ICD 301.83, DSM 301.83 Chronic Fatigue Hou Group -29- This paper scale is applicable to China National Standards (CNS) Α4 specifications (210X 297 mm) (please read the back (Notes to fill out this page) h installed.

、 1T Α7 Β7 Printed by the Consumers Cooperative of the Central Bureau of Economic Affairs of the Ministry of Economy V. Description of Invention (4) Premature ejaculation, DSM 302. 75 Erectile sleepy chicken, DSH 302. 72 Anorexia nervosa, ICD 307.1, DSM 307.10 Sleep disorders, ICD 307. 4 Autism Aphasia is a mad person. I have tested the representative sister compound of the present invention on conscious experimental animals. The amazing results of the test show that the present invention has excellent adhesion. The test is as follows. An Spr ag ue-Da w 1 ey Dabai R (Har I a η or Charles River product) weighing 270-300 g was anesthetized with chloral hydrate / pentobarbital (170 mg 36 mg / kg i.p. , Soluble in 30% malonylase, 14% ethanol) Μ surgical dialysis probe (Perry and Fuller, Effect of fluoxetine on serotonin and dopa η ine concentration in rat hypothalamus after administration of fluoxetine plus L-5-hydroxytryptophan, Life Sc i., 50, 1683-90 (1992)). We use David Kopf to set up β fixation device * Μ equal mouth-1.5 mm, side-1.3 mm and back-9.0 mm to probe the military side to implant the lower visual hill (Paxinos and Watson, 1986). After a 48-hour recovery period, the rats were placed in a large plastic bowl with a rising fluid «rotating system (CHA / 120 鳸 鳳 for free-moving animals, Bioanalytical Systems, Vest Lafayette, IN). Ml.0 microliters / min. The filtered candidate mandibular ridge "CSF" infiltration edge probe (150 bM NaCl, 3.0 · Μ KC1, 1.7 · Μ CaCU and 0.9 MgCU). Ｍ 一 20 微 -30- The size of this paper is easy to use China National Standard (CNS) A4 specification (210X297mm) (please read the precautions on the back before filling in this page) h Pack. Thread 320562 A7 B7 5. Invention Description (Chang) The dialysis solution in the tube is set to the tenport HPLC control valve. After each 30-minute sampling period, the dialysate collected from the wine tube is injected into the analytical column (Spherisorb 3 «0DS2, 2X150 m, Keystone Scientific) ° MPerry and Fuller are printed on the staff consumption cooperative of the Central Rubbing Bureau of the Ministry of Economic Affairs The method (1993) measures monoamines. In other words, the 5-HT, NE, and DA of the dialysate collected in 20 microliter buried tubes were analyzed. Inject a 20 μl of permeable solution into the column with a mobile phase that can resolve ME, DA and 5-HT: 75_ potassium acid, 0.5 · M ethylenediaminetetraacetic acid, 1.4 »M heptanesulfonic acid Sodium and 8% formazan, pH 4.9. Mobile phase M for amine columns. Adjustable pump for flow, initial flow rate 0.2 ml / min, increase to 0.3 μl / min at 5 minutes, then slowly return to 0.2 ml / min at 26 minutes, total flow The time is 30 minutes. The set flow "Cheng K" will dissolve out 5-HT in a 25-minute period. The chemical detector (EC & G, Model 400) of the amine column was set at a potential of 400 uV and a slip sensitivity of 0.2 nA / V. MHevlett-Packard HP1000 color analysis kit collects and analyzes data. It can measure the peak height and calculate the sample concentration. The baseline amount should be at least 90 minutes before application. The de-seedling water of the drug was prepared and applied in the amount of the following results (volume 0.25-0.3 ml). We calculated the amount of extracellular amine in the microdialysate by comparing K with the peak height of 50 picomolar standard solution. The average value of the top four samples of cytopharmaceuticals was used as the reference amount for each experiment and the data was converted into a percentage of the reference amount. The matching t-test M was used to compare the average of the reference value at the time point immediately before the application with the value at each time point thereafter. We have made the data available to make the trend more obvious. 31-The size of this paper is in accordance with China National Standard (CNS) A4 (210X297mm) ---------— Pack—I (please read the precautions on the back before filling this page) .tr line A7 B7 printed by the Employee Consumer Cooperative of the Ministry of Economic Affairs, China Bureau of Standards V. Description of the invention (29) In this test, the sister treatment included the racemic mixture of hydrogenated hydrogen and 4- (2-hydroxy-3-xylhexylamino) Propoxy) indole, flustine of maleic acid. Μ Prepare mice as above and indole (3¾ g / kg) subcutaneously 100 minutes after the start of the experiment. At 210 minutes after the start of the experiment, M 10 «g / kg intraperitoneal administration of flustatin * plus 3 mg / kg of the second thinnest indole. Each data point reported in this article represents a single animal. After the administration of lumbenole, the 5-HT held in the dialysate fell to 50% of the baseline weight, and at 210 minutes it was approximately 80% of the baseline. After flustine was applied, it was stabbed and measured after 240 minutes of sickle, about 410% of the benchmark dai, 270 minutes of sickle was about 450% of the baseline, 300 minutes of sickle was about 46 0%, and at 33 minutes It was about 390% of the baseline. After the application of lumbenole, the amount of NE increased to approximately 180% of the baseline and fell to near baseline at 210 minutes of sickle. After flustine was applied, it increased to approximately 500% of the benchmark shovel at 240 minutes, and was steadily extinguished to 340% and 280% of the benchmark at 270, 300, and 33 minutes. Similarly, the amount of DA increased to approximately 210% of the baseline at 120 minutes and decreased to near baseline at 210 minutes. After fluethin application, the amount of DA was reduced to approximately 1430% of the baseline at 240 minutes, approximately 840% of the baseline at 270 minutes, approximately 530% at 300 minutes, and approximately 330% at 330 minutes. & Μ.2. In this test, the application of the prosthesis is (+) _ durostine, hydrogen chloride * the application amount is 4 mg / kg and (-)-pinduo K. The application is set at 5 mg / kg . The method of this test is the same as that of Test 1. 120 minutes after the start of the test -32- This paper size is applicable to the Chinese National Standard (CNS) Α4 specification (210X297 mm) (please read the $ item on the back and fill in this page) • Packing. A7 B7. 5. Description of the invention (30) Application of (-)-pindol a, then at 210 minutes for duloxetine and the second dose of (-)-pindollen, the amount of application is 5. Mg / kg. The results shown below are the percentages of the three monoamines to the baseline at different times after the start of the test. Each data point represents the average of three or more animals. (Please read the precautions on the back before filling in this page) r Pack and order ELJML 5 ^ ΗΤ HA. 120 minutes 8096 9096 90% 150 90 100 90 180 110 120 70 210 100 110 100 240 240 350 230 270 340 230 170 300 360 210 140 330 — 230 150 360 330 170 150 Employee Cooperative of the Central Bureau of Economic Affairs of the Ministry of Economic Affairs of the People's Republic of China. This test is conducted in the same way as Test 1, using 4- (2-hydroxy-3-cyclohexyl) at 120 minutes Aminopropaneoxy) indole, maleic acid », 3 * g / kg, and (+)-durostatin, gasification 鈥, 4 邂 克 / kg, and the first at 270 minutes Two cocoons of indole, 3 ng / kg. The results were as reported in the above Lanshi test 2. The result of 5-HT is the average of 3 animals, while the other results are the average of 4 animals. Thread · -33- The X degree of this paper is applicable to the Chinese National Standard (CNS) (210X297mm) 320562 A7 B7 V. Description of the invention (Μ) Time 5-HT Mu \ LL 120 points 90¾ 10096 10% 150 130 160 150 180 130 140 130 210 80 140 110 240 90 130 100 270 80 150 110 300 650 580 410 330 670 390 280 360 590 450 240 390 490 320 210 420 440 290 200 (please read the precautions on the back before filling out this page) ·

, 1T Printed by the Employee Consumer Cooperative of the Central Prototype Bureau of the Ministry of Economic Affairs. The paper size is applicable to China National Standards (CNS) A4 (210X297mm)

Claims (1)

8 8 8 8 ABCD 330562 No. 331 丨 0090 Patent application for amendment of the scope of the Chinese patent application (November 1985) VI. Patent scope 丨 t ^ Bulletin 1. A treatment originated from or due to serotonin, polyadrenaline and S-drug compound for diseases caused by reduced dopamine utilization rate, which includes the first ingredient selected from 1 to 80 mg / day of fluoxetine (flU0xetine) and 1 to 30 mg / day of duloxine Duloxetine, venlafaxine from 10 to 150 mg / day and MUilnacipran from 10 to 100 mg / day, and the second ingredient, which is selected from 1 to 6 Pindolol (mg / day), penbutolol (2 to 80 mg / day), propranolol (10 to 240 mg / day), 1 to 100 mg / day (X) , Tertatolol, and 1 to 50 mg / day of a compound of the formula 0H I ·· I Ar-O-CHjCHCHjNHZ where Ar is (please read the precautions on the back before filling this page) R2 is printed by the Uncle Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs. R is nitrogen; Z is (C4_Ce cycloalkyl), KCi-C < t alkyl or phenyl can be substituted if necessary; X is -H; Accept the salt. This paper Sucai H8 materials (CNS) (210 ^: 2 # competition) 320562 Including 8: D8 Six, apply for a patent scope The Central Standards Bureau of the Ministry of Economic Affairs Shoulder Consumer Cooperative printed the packaged diseases and diseases. Sister group, the first phase of the first item, body, perinatal pain, yellow group disease, Fan Houhou Hou Changchang group, divine or syndrome, deficiency, eccentric syndrome, special, is group, after, Intentional illness 'eating disorder and please, don't use it for poisoning, loss of fear and fear, hard work and discomfort ,, Shen > Painful, moderate illness' trauma, dementia, madness, fatigue, Distressed acuity syndrome, according to depression, pre-existing fine grass and worry, recalling the year, the interaction, the dysfunction, the marginal discharge of hydroxysleep, the closed root, the migraine, the diet, the alcohol, the alcohol, the fear, the focus, and the old society. Shenshuizi 1 (Please read the note Ϋ on the back before filling in this page) This paper is again applicable to China National Standards (CNS) A4 specifications (210 ^ 2 is public gray) A8 Sixth, the scope of patent application 320562 is drawn _ crazy. 3. The sister compound according to item 1 of the patent application, which includes dulostatin. 4 'According to the sister compound of item 1 of the scope of the patent application, it includes gastin. 5 The sister compound according to item 1 of the patent application scope, wherein the second type of component is selected from Pindoz and 4- (2-hydroxy-3-cyclohexylaminopropoxy) indole 0 6. According to the application The sister compound of any one of the items 1 to 5 of the patent scope * It is made of M and can enhance the effect of the first class of ingredients to increase the utilization of serotonin, norepinephrine and dopamine in the brain. 7. The composition according to any one of the items 1 to 5 of the patent application scope, which is made of M and can be used for the treatment of diseases caused by or related to the reduced utilization of serotonin, norepinephrine or dopamine. . (Please read the precautions on the back before filling in this VK), 1Τ 4! Central Bureau of Economic Affairs of the Ministry of Economic Affairs w: Printed copies of industrial and consumer cooperatives. The paper size can be used in China National Standards (CNS) Α4 specifications (210 father_29 Duo Gong thin)