CN103396453B - Pharmaceutical use of Pradefovir - Google Patents
Pharmaceutical use of Pradefovir Download PDFInfo
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- CN103396453B CN103396453B CN201310349522.8A CN201310349522A CN103396453B CN 103396453 B CN103396453 B CN 103396453B CN 201310349522 A CN201310349522 A CN 201310349522A CN 103396453 B CN103396453 B CN 103396453B
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Abstract
The invention belongs to the field of medicines, and mainly provides a use of Pradefovir for preparing medicines for treating male patients with hepatitis B but not suitable for women or excluded from use by women. Untoward effects generated by Pradefovir delivery can be reduced or even avoided. In addition, the invention further provides combination of Pradefovir and a second pharmaceutical active component, so that untoward effects can be further reduced.
Description
Technical field
The invention belongs to field of medicaments, particularly, the present invention relates to the purposes of Pradefovir in the medicine of the various reduction side effects of preparation.
Background technology
Pradefovir or its pharmaceutical salts (as, mesylate) be the one in No. 200510098771.X disclosed front drug compound of Chinese patent, the specifically front drug compound of Adefovir (PMEA), it can be metabolized to PMEA in vivo, can be directly used in treatment or prevention of liver disease or metabolic disease, comprise hepatitis B etc.In addition, (our Chinese patent discloses Pradefovir mesylate No. 2012103443337, (+)-cis-9-{2-[4-[(S)-(3-chloro-phenyl-)-2-oxygen-1,3,2 – dioxy phospha six encircle-2-methylene radical]-1-ethyl VITAMIN B4 mesylate) Crystallographic Study achievement.
Along with the progress of arduous clinic study, we have found unexpectedly many results that there is no theoretical foundation or prior art foundation, cannot expected result according to these, by targetedly in the improvement aspect pharmaceutical applications and/or preparation, we have improved medication effect, especially can reduce or the collaborative untoward reaction that reduces medication, be very useful under this environment of day by day drug safety being paid close attention to Yao Jian department and the public.
Summary of the invention
The technical problem to be solved in the present invention is purposes, method and/or the pharmaceutical preparation of the Pradefovir that provides new, is mainly used in reducing untoward reaction.
Particularly, in first aspect, the invention provides purposes or the method for Pradefovir, wherein relate to and be used for the treatment of male sex's hepatitis B patient, but be not suitable for or get rid of women using.Because inventor's research chances on, when administration Pradefovir, can there is headache in the women of half, untoward reaction such as dizzy grade, and the male sex there will be hardly, therefore the medicine of preparing can pass through such as shape, material, color or the preparation itself that wherein the comprised adaptability to masculinity and femininity, select to prepare the medicine that is used for the treatment of male sex's hepatitis B patient but be not suitable for or get rid of women's use, thereby effectively reduce or avoid selecting of women, even can increase selecting of the male sex and do not affect, can objectively obtain and reduce or avoid having a headache, the dizzy unexpected effect that waits untoward reaction.
In this article, term " man " and " female " refer to people's sex, and correspondingly, medicine also refers to the medicine that people uses, and the pharmaceutical preparation (as without contrary instruction, referred to as preparation) comprising in medicine is also the pharmaceutical preparation that people uses.Preferably in the present invention, people is adult, as preferably adult man of the male sex (people), and/or, preferably adult female of women (people).Term " is grown up " and " adult " possesses legal definition in China, in this article all according to the legal definition of China.
In this article, term " be used for the treatment of male sex's hepatitis B patient but be not suitable for or get rid of women use " refer to, pass through technique means, comprise the technique means of the branch of sciences such as pharmaceutics, drug packaging, psychology and study of behaviour, make the technical characterictic of the medicine of preparing can reduce or avoid selecting or using of women, and do not affect selecting or using of (preferably can the increase) male sex, thereby increase the ratio (, reducing or eliminate the ratio of women's hepatitis B patient in the treatment crowd of institute) of male sex's hepatitis B patient in the treatment crowd of institute.
The technical scheme of first aspect present invention can be embodied as Pradefovir for the preparation for the treatment of male sex's hepatitis B patient but be not suitable for or get rid of women use medicine in purposes.
The technical scheme of first aspect present invention also can be embodied as the method for preparation containing the medicine of Pradefovir, and wherein said medicine is used for the treatment of male sex's hepatitis B patient but is not suitable for or gets rid of women using.
Because the inventor finds, treat male sex's hepatitis B patient but be not suitable for or get rid of women using, can reduce or eliminate the ratio of women's hepatitis B patient in the treatment crowd of institute, thereby objectively reduce the caused untoward reaction of Pradefovir (certainly, can keep the effective treatment to hepatitis B) simultaneously.So, the technical scheme of first aspect present invention can also be embodied as Pradefovir for the preparation for the treatment of hepatitis B and reduce untoward reaction (as, headache and/or dizzy) medicine in purposes, wherein hepatitis B is male patient's hepatitis B.Or, the technical scheme of first aspect present invention also can be embodied as the method for preparation containing the medicine of Pradefovir, wherein said medicine be used for the treatment of hepatitis B and reduce untoward reaction (as, headache and/or dizzy), wherein hepatitis B is male patient's hepatitis B.
In this article, term " medicine " has popular familiar implication, even the direct cognitive of the existing medicine of selling from pharmacy, conventionally medicine comprises outer packaging and the pharmaceutical preparation in this outer packaging inside, and optionally it is also included in the internal packing of the inner and direct packaged pharmaceuticals preparation of this outer packaging.
Medicine generally also comprises specification sheets.Wherein, specification sheets also can occur with the label form of outer packaging or internal packing.Because specification sheets can directly be indicated the Gender of used medicine, be used for the treatment of male sex's hepatitis B patient but be not suitable for or get rid of women using thereby realize, so preferably in the present invention, specification sheets is to record the specification sheets that is used for the treatment of male sex's hepatitis B patient but be not suitable for or get rid of women's use.
Based on packaging, psychology and study of behaviour technique means, obtain the outer package product that can realize the technique effect of distinguishing different use crowds in fast-moving consumer goods field, for packaging, the personnel of learning a skill know.In recent years, this technology is also gradually by drug packaging field is used for reference, as to improving for technical characterictics such as the shape (or moulding) of drug purchase person vision visible packaging, color (or color), materials (or material), can be applicable to the preference of different crowd, thereby improve or reduce the ratio that corresponding crowd uses or select (as referring to, pharmaceutical packing designs the impact on consumer psychology. medical Leader, 29(1): 130; Drug packaging and consumer psychology. Shanxi economic management cadre academy journal, 19(3): 16; The demand of drugs Packaging Design to patient's subconsciousness consumer psychology. decorate 202:106; Based on the drugs Packaging Design of consumer psychology. Packaging Engineering, 28(2): 158; The utilization of color in drug packaging. Packaging Engineering, 33(12): 104, etc.).So, the packaging in the preferred medicine of the present invention be used for the treatment of male sex's hepatitis B patient but be not suitable for or get rid of women use packaging.Due to be more directly by buy time visible vision affect selecting or using of different sexes crowd, therefore, the present invention more preferably outer packaging in medicine is be used for the treatment of male sex's hepatitis B patient but be not suitable for or get rid of the outer packaging that women uses, the step of, preparing described in first aspect present invention comprises Pradefovir is packed into and is applicable to male sex's hepatitis B patient but is not suitable for or gets rid of in the outer packaging of women's use.Such outer packaging can entrust professional Packaging Engineering company to obtain by market channel, and for example the form of questionnaire obtains the data of determining packaging feature by inquiry; And for example, by men and women, outer packaging preference difference is manufactured to outer packaging, comprise selection material, manufacture shaping and/or coating color.
By the selection of the dosage form in medicine, also can realize and be applicable to male sex's hepatitis B patient but be not suitable for or get rid of women using.For example, preparation of the present invention is not vagina administration preparation, if not being suppository.Like this, be more not suitable for women's use, and do not affect the male sex's use.
In this article, term " unit formulation " is the abbreviation of unit pharmaceutical preparation, has implication well-known to those skilled in the art, the amount that each unit (as individual, sheet, grain or pin etc.) of described preparation comprises the required active constituents of medicine of single administration.Medicine comprises the unit formulation of one or more units, generally includes the unit formulation of multiple units.
Determine the amount of active drug composition in unit formulation, a step in the process of preparing medicine or pharmaceutical preparation.In order to be applicable to male sex's hepatitis B patient but be not suitable for or get rid of women using, can determine with male individual body weight, but for pharmacy corporation commercial application, conventionally determine with male sex's mean body weight.In the present invention, preferably medicine comprises the unit formulation of one or more units, effective dose × adult man mean body weight of weight=adult per weight of the Pradefovir that each unit formulation contains.In this article, the effective dose of adult's per weight is not distinguished men and women, and adult man mean body weight is greater than grownup's mean body weight (, grownup's mean body weight of not distinguishing men and women of these adult man affiliated areas; Adult man mean body weight certainly (also more) is greater than adult female's mean body weight (, adult female's mean body weight of these adult man affiliated areas).So the weight range of the Pradefovir that each unit formulation of the present invention contains is the preferable range in the fuzzy scope of prior art enlightenment, and the weight of the Pradefovir that contains of preferred each unit formulation is not 5mg, 10mg, 20mg or 30mg.The such numerical value of the latter is without the empirical value obtaining through calculating, and adult man mean body weight is not integer conventionally, so the weight of the Pradefovir that of the present invention each unit formulation that product obtains contains is not integer conventionally yet.For example, according to Data of Civil Constitution Monitoring communique in 2000, the Chinese adult male sex's mean body weight was 67.7kg.
Further, in order personalization or zonule to prepare the needs of medicine, pharmacy corporation can be in drug use region (as, a province), statistics or random sampling obtain the mean body weight of adult man, as can according to medicine prison or medical institutions add up or random sampling.So preferably in a first aspect of the present invention, the step of described preparation comprises,
(1), in drug use region, statistics or random sampling obtain the mean body weight of adult man;
(2) effective dose × adult man mean body weight of weight=adult per weight of the Pradefovir containing with each unit formulation, the weight of the Pradefovir that the each unit formulation of calculating acquisition contains; With
(3) Pradefovir that gets the weight of the Pradefovir that each unit formulation contains makes unit formulation, wherein optionally comprises the process that Pradefovir mixes with pharmaceutically acceptable auxiliary material.
In the prior art, due to personalization or zonule, to prepare medicine seldom universal, so have no the report that has aforesaid method flow process in the process of preparing medicine of Pradefovir.
Further, the step of described preparation can also comprise afterwards in step (3),
(4) unit formulation of one or more units is packaged into medicine process (as, by the unit formulation of one or more units pack into be applicable to male sex's hepatitis B patient but be not suitable for or get rid of women use outer packaging in, form medicine); With
(5) optionally to add in medicine specification sheets (as, record and be used for the treatment of male sex's hepatitis B patient but be not suitable for or get rid of the specification sheets that women uses).
In this article, the effective dose of adult's per weight is not distinguished men and women, so be definite value, is the effective dose that adult's per weight of men and women is not distinguished in drug use region.This dosage can be obtained for entirety (irrespective of sex) sampling test in the region of required input medicine by pharmacy corporation.As in the present invention, according to the difference of ethnic group, the effective dose of adult's per weight is 0.25～0.65mg/kg, and preferably 0.4～0.6mg/kg, is more preferably 0.45～0.55mg/kg, for example, in the specific embodiment of the present invention, can be 0.5mg/kg.
In second aspect, the invention provides the pharmaceutical preparation for the treatment of hepatitis B patient, it comprises Pradefovir and the second active constituents of medicine, and pharmaceutically acceptable auxiliary material, and wherein the second active constituents of medicine is not KETOKONAZOL, Rifampin or erythromycin.The inventor studies discovery, and KETOKONAZOL, Rifampin or erythromycin can suppress Pradefovir metabolism and go out activeconstituents, affect drug effect, or increase suddenly the metabolic activity of Pradefovir, cause drug safety hidden danger, therefore gets rid of and uses.
The technical scheme of second aspect present invention also can be presented as Pradefovir and the second active constituents of medicine combine for the preparation for the treatment of hepatitis B patient pharmaceutical preparation in purposes, wherein the second active constituents of medicine is not KETOKONAZOL, Rifampin or erythromycin.
The second active constituents of medicine can be the active constituents of medicine that can not treat hepatitis B.Under not being bound by any theory restrictions, the inventor found surprisingly, and antacid can reduce the untoward reaction of Pradefovir, especially the untoward reaction of female patient.So preferably, in a second aspect of the present invention, the second active constituents of medicine is antacid, preferably alkaline calcium salt, as calcium carbonate.In this article, the pharmaceutical preparation that term " antacid " refers to can neutralizing acid (as, hydrochloric acid in gastric juice).There is at present multiple antacid list marketing, as
deng.
In unit formulation, the weight of Pradefovir can be applicable to all Adult Groups, therefore preferably determines with effective dose × grownup mean body weight of adult's per weight, preferably can determine according to first aspect present invention.And in unit formulation, the weight of antacid can be applicable to all Adult Groups, therefore also preferably determine with effective dose (for example, as 0.25～0.4mL/kg, preferably 0.3～0.35mL/kg, 0.33mL/kg) × grownup's mean body weight of adult's per weight.
In addition, also preferred agents preparation is oral preparations, for example tablet or capsule.
In the third aspect, the invention provides adult man mean body weight, obtain the method (as in drug use region, statistics or random sampling obtain the mean body weight of adult man) of the mean body weight of adult man and/or applicable male sex's hepatitis B patient but be not suitable for or get rid of the purposes of the outer packaging that women uses.
The method that the technical scheme of third aspect present invention can be embodied as the mean body weight of adult man mean body weight or acquisition adult man contains the purposes in the medicine of Pradefovir in preparation.
The technical scheme of third aspect present invention also can be embodied as the method for preparation containing the medicine of Pradefovir, and it comprises the method that uses adult man mean body weight or comprise the mean body weight that obtains adult man.
The technical scheme of third aspect present invention can also be embodied as be applicable to male sex's hepatitis B patient but be not suitable for or get rid of outer packaging that women uses in preparation containing the purposes in the medicine of Pradefovir.
Or the technical scheme of third aspect present invention also can be embodied as the method for preparation containing the medicine of Pradefovir, it comprises the outer packaging that uses applicable male sex's hepatitis B patient but be not suitable for or get rid of women's use.
Feature in these purposes or method is the aforesaid preferred feature of this paper preferably, for example can comprise, described medicine is used for the treatment of male sex's hepatitis B patient but is not suitable for or gets rid of women using, or, described medicine be used for the treatment of hepatitis B and reduce untoward reaction (as, headache and/or dizzy), wherein hepatitis B is male patient's hepatitis B, etc.
The present invention has following beneficial effect: keep drug effect, but can reduce or the collaborative untoward reaction that reduces medication, got rid of potential reduction drug effect or caused the medicine of safety issue; Obtain the required cost of above-mentioned effect low, prepare medicine process convenient.
For the ease of understanding, below will be described in detail the present invention by specific embodiment.It needs to be noted, these descriptions are only exemplary descriptions, do not form limitation of the scope of the invention.According to the discussion of this specification sheets, many variations of the present invention, change are all apparent concerning one of ordinary skill in the art.
In addition, the present invention has quoted open source literature, and these documents are in order more clearly to describe the present invention, and their full text content is all included in and carried out reference herein, just looks like that repeated description is excessively the same in this article for their full text.
Embodiment
Further illustrate by the following examples content of the present invention.As do not specialize, the clinical trial means that in embodiment, technique means used is well known to those skilled in the art, can open guide to drug approval etc. referring to drug regulatory department's (as, SFDA).
Embodiment 1 clinical safety test:
Under the license of drug regulatory department, to random 24 adult experimenters (12 male sex and 12 women), in the Pradefovir mesylate of the 1st day oral 0.5mg/kg dosage (in Pradefovir itself) under empty stomach situation.From the-1 day, all experimenters can not leave clinical study mechanism, until safety evaluation finishes.Carry out during this time every medicine for test, and observe clinical response; 12 asian population adult experimenters of random assignment (6 male sex and 6 women) take placebo the same period in addition, as negative control group.
Result according to body weight after to data normalization shows, the Cmax of Pradefovir mesylate and AUC in the serum of female subjects
0-96hgeometric mean is respectively than respectively low 6% and 12% of male subject, Cmax and the AUC of (metabolism of Pradefovir mesylate produces) PMEA in female subjects
0-96hgeometric mean is respectively than male subject low 9% and 6%, but, the renal clearance (CLR) of Pradefovir mesylate in female subjects and PMEA is but respectively than male subject low 21% and 11%, and the clinical adverse of observing is headache or dizzy (7/24,29%; In negative control group, men and women does not observe headache and dizzy), wherein female subjects occur to have a headache or dizzy frequency (6/12,50%) far away higher than male subject (1/12,8%).
In test, do not report death and serious adverse reaction, and compared with negative control group, significant result and Sexual-related trend clinically are not all found in other vital signs and physical examination etc.
The clinical test of pesticide effectiveness of embodiment 2:
Under the license of drug regulatory department, random adult experimenter (is disregarded to (majority is women) of exiting because of untoward reaction, final 50 hepatitis B patients altogether effectively participate in test), every day oral 0.5mg/kg dosage under empty stomach situation Pradefovir mesylate, continue altogether to take 48 weeks, then cut out, every 4-8 weeks once make a house call during this time; In addition random adult experimenter (disregard because of untoward reaction and exit, finally amount to 9 hepatitis B patients and effectively participate in test) is taken to adefovir ester the same period, as positive controls.
Result shows, in the making a house call of the 24th week and the 48th week, can't detect blood plasma HBV DNA(level and be less than 10 in the experimenter that employing Pradefovir mesylate is treated
-6the instrument limit of detection of/mL) experimenter's ratio be respectively 72% and 80%, in the experimenter of adefovir ester treatment, can't detect blood plasma HBV DNA ratio and be respectively 33% and 44% and adopt.
The Combined Preparation test of embodiment 3Pradefovir and antacid:
Under the license of drug regulatory department, to random 16 adult experimenters (8 male sex and 8 women), in the 1st day the Pradefovir mesylate of oral 0.5mg/kg dosage and 0.33mL/kg dosage simultaneously under empty stomach situation
calcium carbonate oral liquid (can purchased from Johnson Co.).From the-1 day, all experimenters can not leave clinical study mechanism, until off-test.Carry out during this time every medicine generation and efficacy testing, and observe clinical response.
Result shows, associating
administration, does not have significant difference with the efficiency assay result of the individually dosed Pradefovir mesylate of embodiment 2, show drug effect not can because of with
combined Preparation and improving; Compared with the test-results of the individually dosed Pradefovir mesylate of embodiment 1,
combined Preparation does not affect for producing significantly the medicine of Pradefovir mesylate itself, but makes the AUC of the PMEA of its metabolism generation
0-infthe 90%CI(67.0 of geometric mean ratio, 86.4) drop on 80-125% completely without under effect border, and the 90%CI(77.5 of Cmax ratio, 108.8) overlapping with 80% lower limit, show
combined Preparation is on exposing and have clinical significant impact PMEA; And after Combined Preparation, headache occurs female subjects or dizzy frequency (2/8,25%) also declines greatly with respect to the individually dosed of embodiment 1, the male sex does not report headache, makes to be more applicable to patient (especially women) medication safely.
The Combined Preparation test (comparative example) of embodiment 4Pradefovir and KETOKONAZOL or Rifampin, erythromycin
Process is basic identical in the method for embodiment 3, and difference is KETOKONAZOL, the Rifampin of 10mg/kg dosage or the erythromycin of 8.3mg/kg dosage that antacid is replaced by respectively 6.7mg/kg dosage.
Result shows, Pradefovir mesylate and KETOKONAZOL Combined Preparation, make respectively AUC and the Cmax of Pradefovir mesylate increase by 348% and 250%, but but make respectively the AUC of PMEA and Cmax reduce by 84.8% and 92.4%, owing to being difficult to the PMEA of metabolism generation significant quantity, therefore test is ended; Pradefovir mesylate and Rifampin Combined Preparation, make respectively AUC and the Cmax of Pradefovir mesylate reduce by 84.7% and 75.9%, but but make respectively the AUC of PMEA and Cmax increase by 52% and 224%, owing to may causing safety issue, therefore test is ended; Pradefovir mesylate and erythromycin Combined Preparation, make respectively Pradefovir mesylate AUC and Cmax increased about 285% and 253%, but but make respectively the AUC of PMEA and Cmax reduce by 22.7% and 25.3%, the significant quantity of estimating former Pradefovir has been difficult to support drug effect, and therefore test is ended.
The sex preference of embodiment 5Pradefovir medicine outer packaging is selected test:
Owing to also there is no so far Pradefovir marketing drugs, so also there is no the outer packaging of existing Pradefovir medicine.We entrust Xi'an Package Design company to carry out potential consumer (HBV carrier, no matter whether have clinical symptom) outer packaging preference is tested, to reduce women (patient's) preference as far as possible, and do not affect the preference that even meets the male sex (patient), reduce purchase, the usage quantity of female patient with this, increase male patient's purchase, usage quantity, thus the generating capacity of the untoward reactions such as the reduction patient's that uses headache.
Preference test is undertaken by figure and survey form in kind, be to treat the medicine of disease aspect its liver or potential disease and be to have can select to substitute medicine in the case of informing, to the shape of outer packaging, color and material are investigated, select positive, neutrality and negative preferences, add up scoring, reclaim altogether 325 parts of effective questionnaires (137 parts of men, 188 parts of female), result is as shown in table 1 below, show that men and women is still larger to the preference difference of different outer packagings, therefore can be according to table 1, choose between men and women's property preference difference large and be conducive to the packaging feature that the male sex selects, as cool colour area accounts for 70%～100% of the total area, and warm colour area accounts for 30%～0% of the total area.
The preference survey table (in bracket be scoring be positive, neutral, negative number, predilection grade with front exceed negative number shared overall ratio calculate) of the potential men and women patient of table 1 to different outer packagings
Claims (116)
1.Pradefovir for the preparation for the treatment of male sex's hepatitis B patient but be not suitable for or get rid of women use medicine in purposes.
2. purposes claimed in claim 1, wherein medicine comprises specification sheets, this specification sheets is to record the specification sheets that is used for the treatment of male sex's hepatitis B patient but be not suitable for or get rid of women's use.
3. purposes claimed in claim 1, wherein said medicine comprises the unit formulation of one or more units, effective dose × adult man mean body weight of weight=adult per weight of the Pradefovir that each unit formulation contains, wherein adult man mean body weight is greater than grownup's mean body weight.
4. purposes claimed in claim 3, wherein adult man mean body weight is greater than adult female's mean body weight.
5. purposes claimed in claim 3, wherein adult man mean body weight is not integer.
6. purposes claimed in claim 3, the effective dose of wherein said adult's per weight is the effective dose that adult's per weight of men and women is not distinguished in drug use region.
7. purposes claimed in claim 1, the step of wherein said preparation comprises,
(1), in drug use region, statistics or random sampling obtain the mean body weight of adult man;
(2) effective dose × adult man mean body weight of weight=adult per weight of the Pradefovir containing with each unit formulation, the weight of the Pradefovir that the each unit formulation of calculating acquisition contains; With
(3) Pradefovir that gets the weight of the Pradefovir that each unit formulation contains makes unit formulation, wherein optionally comprises the process that Pradefovir mixes with pharmaceutically acceptable auxiliary material.
8. purposes claimed in claim 1, the step of wherein said preparation comprises Pradefovir is packed into and is applicable to male sex's hepatitis B patient but is not suitable for or gets rid of in the outer packaging of women's use.
9. purposes claimed in claim 1, the outer packaging of wherein said medicine be applicable to male sex's hepatitis B patient but be not suitable for or get rid of women use outer packaging.
10. the purposes described in claim 8 or 9, wherein the shape of outer packaging is rectangle.
Purposes described in 11. claims 8 or 9, wherein the shape of outer packaging is square.
Purposes described in 12. claims 8 or 9, wherein the material of outer packaging is metal or papery.
Purposes described in 13. claims 8 or 9, wherein the material texture of outer packaging is metal-like or papery texture.
Purposes described in 14. claims 8 or 9, wherein the coating color of outer packaging be cool colour area account for the total area 70%～100%, and warm colour area accounts for 30%～0% of the total area, or the coating color of outer packaging is full warm colour.
15. purposes claimed in claim 1, wherein medicine is used for the treatment of hepatitis B and reduces untoward reaction.
Purposes described in 16. claims 15, wherein untoward reaction is headache and/or dizzy.
17. purposes claimed in claim 3, wherein said preparation is not vagina administration preparation.
Purposes described in 18. claims 17, wherein said preparation is not suppository.
19. purposes claimed in claim 3, wherein said preparation comprises Pradefovir and the second active constituents of medicine, and pharmaceutically acceptable auxiliary material, and wherein the second active constituents of medicine is antacid.
Purposes described in 20. claims 19, wherein said preparation is by Pradefovir and the second active constituents of medicine, and pharmaceutically acceptable auxiliary material composition, and wherein the second active constituents of medicine is antacid.
Purposes described in 21. claims 19 or 20, wherein the second active constituents of medicine is alkaline calcium salt.
Purposes described in 22. claims 21, wherein the second active constituents of medicine is calcium carbonate.
23. purposes claimed in claim 1, wherein pharmaceutical packing can reduce or avoid selecting or using of women, and does not affect selecting or using of the male sex.
24. purposes claimed in claim 1, wherein pharmaceutical packing can reduce or avoid selecting or using of women, and can increase selecting or using of the male sex.
Purposes described in 25. claims 1,8 or 9, wherein the male sex is adult man.
Purposes described in 26. claims 25, wherein adult man is China's adult man.
Purposes described in 27. claims 1,8 or 9, wherein women is adult female.
Purposes described in 28. claims 25, wherein adult female is China adult female.
The purposes of 29.Pradefovir in the medicine for the preparation for the treatment of hepatitis B and reduction untoward reaction, wherein hepatitis B is male patient's hepatitis B.
Purposes described in 30. claims 29, wherein untoward reaction is headache and/or dizzy.
Purposes described in 31. claims 29, wherein medicine comprises specification sheets, this specification sheets is to record the specification sheets that is used for the treatment of male sex's hepatitis B patient but be not suitable for or get rid of women's use.
Purposes described in 32. claims 29, wherein said medicine comprises the unit formulation of one or more units, effective dose × adult man mean body weight of weight=adult per weight of the Pradefovir that each unit formulation contains, wherein adult man mean body weight is greater than grownup's mean body weight.
Purposes described in 33. claims 32, wherein adult man mean body weight is greater than adult female's mean body weight.
Purposes described in 34. claims 32, wherein adult man mean body weight is not integer.
Purposes described in 35. claims 32, the effective dose of wherein said adult's per weight is the effective dose that adult's per weight of men and women is not distinguished in drug use region.
Purposes described in 36. claims 29, the step of wherein said preparation comprises,
(1), in drug use region, statistics or random sampling obtain the mean body weight of adult man;
(2) effective dose × adult man mean body weight of weight=adult per weight of the Pradefovir containing with each unit formulation, the weight of the Pradefovir that the each unit formulation of calculating acquisition contains; With
(3) Pradefovir that gets the weight of the Pradefovir that each unit formulation contains makes unit formulation, wherein optionally comprises the process that Pradefovir mixes with pharmaceutically acceptable auxiliary material.
Purposes described in 37. claims 29, the step of wherein said preparation comprises Pradefovir is packed into and is applicable to male sex's hepatitis B patient but is not suitable for or gets rid of in the outer packaging of women's use.
Purposes described in 38. claims 29, the outer packaging of wherein said medicine be applicable to male sex's hepatitis B patient but be not suitable for or get rid of women use outer packaging.
Purposes described in 39. claims 37 or 38, wherein the shape of outer packaging is rectangle.
Purposes described in 40. claims 37 or 38, wherein the shape of outer packaging is square.
Purposes described in 41. claims 37 or 38, wherein the material of outer packaging is metal or papery.
Purposes described in 42. claims 37 or 38, wherein the material texture of outer packaging is metal-like or papery texture.
Purposes described in 43. claims 37 or 38, wherein the coating color of outer packaging be cool colour area account for the total area 70%～100%, and warm colour area accounts for 30%～0% of the total area, or the coating color of outer packaging is full warm colour.
Purposes described in 44. claims 32, wherein said preparation is not vagina administration preparation.
Purposes described in 45. claims 44, wherein said preparation is not suppository.
Purposes described in 46. claims 32, wherein said preparation comprises Pradefovir and the second active constituents of medicine, and pharmaceutically acceptable auxiliary material, and wherein the second active constituents of medicine is antacid.
Purposes described in 47. claims 32, wherein said preparation is by Pradefovir and the second active constituents of medicine, and pharmaceutically acceptable auxiliary material composition, and wherein the second active constituents of medicine is antacid.
Purposes described in 48. claims 46 or 47, wherein the second active constituents of medicine is alkaline calcium salt.
Purposes described in 49. claims 48, wherein the second active constituents of medicine is calcium carbonate.
Purposes described in 50. claims 29, wherein pharmaceutical packing can reduce or avoid selecting or using of women, and does not affect selecting or using of the male sex.
Purposes described in 51. claims 29, wherein pharmaceutical packing can reduce or avoid selecting or using of women, and can increase selecting or using of the male sex.
Purposes described in 52. claims 29,37 or 38, wherein the male sex is adult man.
Purposes described in 53. claims 52, wherein adult man is China's adult man.
Purposes described in 54. claims 37 or 38, wherein women is adult female.
Purposes described in 55. claims 54, wherein adult female is China adult female.
56. preparations are containing the method for the medicine of Pradefovir, and wherein said medicine is used for the treatment of male sex's hepatitis B patient but is not suitable for or gets rid of women's use, and the step of wherein said preparation comprises,
(1), in drug use region, statistics or random sampling obtain the mean body weight of adult man;
(2) effective dose × adult man mean body weight of weight=adult per weight of the Pradefovir containing with each unit formulation, the weight of the Pradefovir that the each unit formulation of calculating acquisition contains; With
(3) Pradefovir that gets the weight of the Pradefovir that each unit formulation contains makes unit formulation, wherein optionally comprises the process that Pradefovir mixes with pharmaceutically acceptable auxiliary material.
Method described in 57. claims 56, the effective dose of wherein said adult's per weight is the effective dose that adult's per weight of men and women is not distinguished in drug use region.
Method described in 58. claims 56, the step of wherein said preparation also comprises Pradefovir is packed into and is applicable to male sex's hepatitis B patient but is not suitable for or gets rid of in the outer packaging of women's use.
Method described in 59. claims 58, wherein the shape of outer packaging is rectangle.
Method described in 60. claims 58, wherein the shape of outer packaging is square.
Method described in 61. claims 58, wherein the material of outer packaging is metal or papery.
Method described in 62. claims 58, wherein the material texture of outer packaging is metal-like or papery texture.
Method described in 63. claims 58, wherein the coating color of outer packaging be cool colour area account for the total area 70%～100%, and warm colour area accounts for 30%～0% of the total area, or the coating color of outer packaging is full warm colour.
Method described in 64. claims 56, wherein pharmaceutical packing can reduce or avoid selecting or using of women, and does not affect selecting or using of the male sex.
Method described in 65. claims 56, wherein pharmaceutical packing can reduce or avoid selecting or using of women, and can increase selecting or using of the male sex.
Method described in 66. claims 56, wherein said preparation is not vagina administration preparation.
Method described in 67. claims 56, wherein said preparation is not suppository.
Method described in 68. claims 56, wherein said preparation comprises Pradefovir and the second active constituents of medicine, and pharmaceutically acceptable auxiliary material, and wherein the second active constituents of medicine is antacid.
Method described in 69. claims 56, wherein said preparation is by Pradefovir and the second active constituents of medicine, and pharmaceutically acceptable auxiliary material composition, and wherein the second active constituents of medicine is antacid.
Method described in 70. claims 68 or 69, wherein the second active constituents of medicine is alkaline calcium salt.
Method described in 71. claims 70, wherein the second active constituents of medicine is calcium carbonate.
Method described in 72. claims 56, wherein said medicine is used for the treatment of hepatitis B and reduces untoward reaction.
Method described in 73. claims 72, wherein untoward reaction is headache and/or dizzy.
Method described in 74. claims 56, the step of described preparation can also comprise afterwards in step (3),
(4) unit formulation of one or more units is packaged into the process of medicine; With
(5) in medicine, add specification sheets.
Method described in 75. claims 74, wherein step (4) is that the unit formulation of one or more units is packed into and is applicable to male sex's hepatitis B patient but is not suitable for or gets rid of in the outer packaging of women's use, forms medicine.
Method described in 76. claims 5574, wherein the specification sheets in step (5) is to record the specification sheets that is used for the treatment of male sex's hepatitis B patient but be not suitable for or get rid of women's use.
Method described in 77. claims 56,64 or 65, wherein the male sex is adult man.
Method described in 78. claims 77, wherein adult man is China's adult man.
Method described in 79. claims 56,64 or 65, wherein women is adult female.
Method described in 80. claims 79, wherein adult female is China adult female.
The pharmaceutical preparation of 81. treatment hepatitis B patients, it comprises Pradefovir and the second active constituents of medicine, and pharmaceutically acceptable auxiliary material, and wherein the second active constituents of medicine is antacid.
Pharmaceutical preparation described in 82. claims 81, it is by Pradefovir and the second active constituents of medicine, and pharmaceutically acceptable auxiliary material composition, and wherein the second active constituents of medicine is antacid.
Pharmaceutical preparation described in 83. claims 81 or 82, wherein the second active constituents of medicine is alkaline calcium salt.
Pharmaceutical preparation described in 84. claims 83, wherein the second active constituents of medicine is calcium carbonate.
85.Pradefovir and the second active constituents of medicine are combined the purposes in the pharmaceutical preparation for the preparation for the treatment of hepatitis B patient, and wherein the second active constituents of medicine is antacid.
Purposes described in 86. claims 85, wherein the second active constituents of medicine is alkaline calcium salt.
Purposes described in 87. claims 86, wherein the second active constituents of medicine is calcium carbonate.
Purposes described in 88. claims 85, wherein said pharmaceutical preparation is arbitrary described pharmaceutical preparation of claim 81～84.
The method of the mean body weight of 89. adult man mean body weights or acquisition adult man contains the purposes in the medicine of Pradefovir in preparation.
Purposes described in 90. claims 89, wherein adult man mean body weight is greater than adult female's mean body weight.
Purposes described in 91. claims 89, wherein adult man mean body weight is not integer.
Purposes described in 92. claims 89, the method that wherein obtains the mean body weight of adult man is in drug use region, statistics or random sampling obtain the mean body weight of adult man.
Purposes described in 93. claims 89, the step of wherein said preparation comprises,
(1), in drug use region, statistics or random sampling obtain the mean body weight of adult man;
(2) effective dose × adult man mean body weight of weight=adult per weight of the Pradefovir containing with each unit formulation, the weight of the Pradefovir that the each unit formulation of calculating acquisition contains; With
(3) Pradefovir that gets the weight of the Pradefovir that each unit formulation contains makes unit formulation, wherein optionally comprises the process that Pradefovir mixes with pharmaceutically acceptable auxiliary material.
Purposes described in 94. claims 93, the effective dose of wherein said adult's per weight is the effective dose that adult's per weight of men and women is not distinguished in drug use region.
Purposes described in 95. claims 93, the step of wherein said preparation also comprises Pradefovir is packed into and is applicable to male sex's hepatitis B patient but is not suitable for or gets rid of in the outer packaging of women's use.
Purposes described in 96. claims 89, wherein medicine is used for the treatment of hepatitis B and reduces untoward reaction.
Purposes described in 97. claims 96, wherein untoward reaction is headache and/or dizzy.
Purposes described in 98. claims 93, wherein said preparation is not vagina administration preparation.
Purposes described in 99. claims 93, wherein said preparation is not suppository.
Purposes described in 100. claims 93, wherein said preparation is arbitrary described pharmaceutical preparation of claim 81～84.
Purposes described in 101. claims 89, wherein adult man is China's adult man.
102. be applicable to male sex's hepatitis B patients but be not suitable for or get rid of outer packaging that women uses in preparation containing the purposes in the medicine of Pradefovir.
Purposes described in 103. claims 102, wherein said medicine is used for the treatment of hepatitis B and reduces untoward reaction.
Purposes described in 104. claims 103, wherein untoward reaction is headache and/or dizzy.
Purposes described in 105. claims 102, the step of wherein said preparation also comprises Pradefovir is packed into and is applicable to male sex's hepatitis B patient but is not suitable for or gets rid of in the outer packaging of women's use.
Purposes described in 106. claims 105, wherein the shape of outer packaging is rectangle.
Purposes described in 107. claims 105, wherein the shape of outer packaging is square.
Purposes described in 108. claims 105, wherein the material of outer packaging is metal or papery.
Purposes described in 109. claims 105, wherein the material texture of outer packaging is metal-like or papery texture.
Purposes described in 110. claims 105, wherein the coating color of outer packaging be cool colour area account for the total area 70%～100%, and warm colour area accounts for 30%～0% of the total area, or the coating color of outer packaging is full warm colour.
Purposes described in 111. claims 102, wherein pharmaceutical packing can reduce or avoid selecting or using of women, and does not affect selecting or using of the male sex.
Purposes described in 112. claims 102, wherein pharmaceutical packing can reduce or avoid selecting or using of women, and can increase selecting or using of the male sex.
Purposes described in 113. claims 102 or 105, wherein the male sex is adult man.
Purposes described in 114. claims 113, wherein adult man is China's adult man.
Purposes described in 115. claims 102 or 105, wherein women is adult female.
Purposes described in 116. claims 115, wherein adult female is China adult female.
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| CN102827206A (en) * | 2012-09-17 | 2012-12-19 | 西安新通药物研究有限公司 | Pradefovir crystal |
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