TW572759B - Pharmaceutical composition comprising lamivudine, zidovudine and a glidant - Google Patents

Description

572759

V. Description of the Invention (The present invention relates to a novel pharmaceutical composition in a single dosage form, which is a combination of the drugs lamivudine and zidovudme, and can be used to treat mammals, including humans. The present invention relates to a single: dosage form of a new type of pharmaceutical composition composed of a combination of the pharmaceuticals lamivudine and chitofidine, which is effective in treating mammalian diseases including humans. The inventions used to treat viral infections are particularly 'infected with reverse green virus, including human immunodeficiency virus (HIV) infections. Human immunodeficiency virus infections can cause a variety of clinical diseases, including acquired immune deficiency Symptoms (AIDS) and chronic neuropathy, recently = advances in the use of multi-drug therapies have led to unexpected improvements in the treatment of human immunodeficiency virus infected patients. Before these multi-drug therapies, generally only Single-drug therapy with limited effects can be used. Single-drug therapy requires a longer treatment time, so the chance of first-time use of tadpoles increases, and Drug therapy is particularly susceptible to mutations in the human immunodeficiency virus to produce drug-resistant species. 0. The use of multi-drug therapy can reduce the chance of human immunodeficiency virus producing resistant variants, because one drug often eliminates the other =

Lg t mutants, multi-drug therapy can even inhibit the replication of human immunodeficiency virus in time, so that the body can clear the human virus. And &amp; <The new multi-drug therapy in the treatment of human immunodeficiency disease 4 infections, patients usually have to cooperate with complex drug delivery methods to succeed, such as every day -4- paper size CNS) ^ (210χ- ^ (Please read the precautionary page on the back first). Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 572759 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 __ 丨 _B7 V. Description of Invention (2). Must be taken Many different medicaments, the interval between medications should be accurate, and the coordination between three meals or diet should be paid attention to. Under this complicated administration method, the patient's mismatch is a well-known problem. Please refer to the appendix Goodman & Gilman · The Pharmacological Basis of Therapeutics Ninth Edition, pages 1704-1705 (1996), in the treatment of human immunodeficiency virus infection, patient non-compliance is an important issue The problem is that non-compliance with the method of administration can cause the human immunodeficiency virus to produce multi-drug resistant variants. Multi-agent therapy in human immunodeficiency virus Among the many compounds commonly used in the method, there are two kinds of chitofidine and lamivudine. The chemical name of lamivudine (also known as 3TCtm) is (2R, cis) -4 -amino-1- (2-hydroxy Methyl-1,3-oxothiol-5-yl)-(1Η) -pyrimidin-2-one, also known as (-)-2 ', 3, dideoxy, 3 · thiocytosine nuclear pyrene Is a kind of synthetic nuclear tadpole. Lamifidine has been proven to have antiviral activity against human immunodeficiency virus and other viruses, such as hepatitis B virus. Kang's products EPIVIR ™, lamivudine and its effect on human immunodeficiency virus are described in EP 03 82526 and W091 / 17159, and the crystal form of lamivudine is also described in W092 / 21676. Phenidine and other reverse transcription pyrene inhibitors, especially chitofidine, are described in WO92 / 20344. Chitofidine chemical name is 3, azido-3 deoxythymidine, is a kind of shouting Nucleic acid, a commercially available kitolidine drug, Glaxo Wellcome product RETROVIRTM, is used for the treatment of human immunodeficiency virus and other viral infections. Refer to the US Patent No. ___- 5-_ listed in the appendix. This paper size is applicable to the Chinese National Standard (CNS) A4 (210X297 mm) 572759 'Invention Note (Argon, for Chidofidine')-^ 1 ^ ^ -4,837, — January 1995, +0 stations "and Qidofidine were used together as °° adults and; ^ speed ^ quasi-lammy, at the time of infection: the first-line treatment drug, lamifidine It has unexpected advantages when used in combination with inhibitors of its viral replication.,,, And θ, especially when used in combination with Qi Mu Fei, in the main clinical trial, the control group has a similar effect on ^: Multiplying effects, # ~ ,,,,,,,,, and 'shown together and used Lamifidine and Qi Duo Yi Yi can effectively delay human Guilu &lt;, Beimmunity and deficiency &lt; Mutant strains. Segregation of king components in medicines or knives (segregati〇 small is a recognized problem, which will cause the main components in the final product to be unevenly dispersed. The main factors that cause segregation include particle size, shape, and density. When multiple active ingredients are combined, and the density or particle size of each active ingredient is different from each other, separation is a difficult problem in a single homogeneous lozenge. In the past, it was used to make mixed formulations of lamivudine and chitofidine. In the case of tablets, the problem of segregation is already an indisputable fact. Even if it can be homogeneously mixed in the initial stage, the main components are separated before the processing process and the tableting. Sliding agents are some traditionally used to improve the particles and powder. Liquid substances because they can reduce the friction between particles, please refer to the appendix Lieberman, Lachman, & Schwartz, Pharmaceutical Dosage Forms: Tablets, Volume 1, pages 177-178 (1989), the sliding agent is generally added before the ingot, so as to promote the flow of particulate matter into the ingot mold of the injecting machine, the sliding agent includes colloidal 2-6-paper Scale applicable Chinese National Standard (CNS) A4 size (210X297 mm) Please first read back ί matters then f p.

• J, Order Impression Consumer Cooperative Cooperative Impressions of the Central Bureau of Standards of the Ministry of Economic Affairs 572759 A7 B7 Five Invention Notes (4 Silica, Sodium Asbestos Talc, Sodium Aluminum Silicate, Calcium Silicate, Powdered Cellulose ', Crystal Cellulose, Corn starch, steel benzoate, carbonic acid, magnesium carbonate, is a kind of stearates, calcium stearate, magnesium stearate, zinc stearate, stearowet C, dian powder, starch 1500, magnesium lauryl sulfate, Or in the study of segregation of pharmaceutical composition, it has been unexpectedly discovered that alpha motile has the effect of improving and promoting the uniformity of the mixture. The novel composition of the invention is During the process, a sliding agent is added to achieve the effect of maintaining the uniformity of the main ingredients. Therefore, one of the objects of the present invention is to develop a method that can simultaneously add the main ingredients lamamidine and chitofidine, or these ingredients And a method for applying such a pharmaceutical prescription. A further object of the present invention is to apply a sliding agent to reduce the medical During the processing of the composition before the tableting, the problem of the separation of the main components occurs. A further object of the present invention is to develop a method that can simultaneously add the main ingredients Dolan Mifedipine and Chitofidine, or these components. Medically acceptable prescriptions printed by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Economic Development and using a pharmaceutically acceptable slip agent can be made into a mixture with homogeneity that meets medical needs. Another object of the present invention is to develop a A pharmaceutical prescription consisting of lamivudine and chitofidine or a pharmaceutically acceptable derivative of these two ingredients, and one or more pharmaceutically acceptable carriers (excipients) are added to the prescription at the same time. If necessary, other therapeutic or preventive medicines can be added, but these carriers must be compatible with other ingredients in the prescription. This paper is suitable for this paper (CNSTA «(210X297 ^) B7 V. Description of the invention (5), And it will not harm the drug users. Another object of the present invention is to use a sufficient amount of chitofidine and chitofidine, or these two ingredients The medically acceptable system can improve the compliance of patients with medications, which can simplify the treatment of human immunodeficiency virus or other virus-infected patients, as demonstrated by the following description of the invention. The present invention provides a pharmaceutical composition comprising: a) a full and effective therapeutic amount of lamivudine or a pharmaceutically acceptable derivative thereof; b) a safe and effective therapeutic amount of chitofidine or a pharmaceutically acceptable amount thereof Acceptable derivatives thereof; and c) pharmaceutically acceptable slip agents. The "safe and effective therapeutic amount" referred to in the present invention refers to an amount of a drug, compound, composition, preparation or medicament, which is sufficient to produce elimination, correction or =, human or other mammalian effects, and will not affect the use of These drugs or medicaments cause serious harm to the mammalian body tissues. The "cooperatively-derived derivatives" referred to in the present invention are printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Drops and refer to any available (direct or indirect) ) The pharmaceutically acceptable salts, hydrates, esters, or salts of the esters, or other compounds suitable for use by the user of the main ingredient or molecular group of a pharmacologically effective metabolite. The invention refers to the "safe and effective treatment", which refers to the amount of a drug required to produce the functions expected by researchers or physicians without causing serious harm to the body tissues of mammals using these drugs. . In addition, the present invention provides a method for treating, reversing, relieving or -8- This paper size is applicable to Chinese National Standard (CNS) A4 specifications (21〇 &gt; &lt; 297 公 楚 572759 A7

Infection of a retroviral prion ', particularly to mammals, especially human epidemic deficiency virus, comprises administering to the animal a safe and effective therapeutic amount of a composition made according to the present invention. The present invention provides a mixture of unidentified or pharmaceutically acceptable other organisms, chistilidine or medicament, in the manufacture of retroviral viruses, especially humans: immunodeficiency virus infections. The use of derivatives (and its derivatives and-pharmaceutically acceptable slip agents). Those who specialize in this technique should be able to recognize the term "treatment" mentioned in this article, which can be extended to a certain-clear disease, The prevention and medical treatment of money or its symptoms. The Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs printed the present invention &lt; The composition contains a safe and sufficient therapeutic dose of 3, _azido-3'-deoxythymine (odd Dofidine) and pharmaceutically acceptable salts 'hydrates, esters, or salts of the esters, and a safe and sufficient therapeutic dose of (+ 2', 3'_dideoxy, 3 _ Thiocytosine nuclear pyramidine (lamivudine) and pharmaceutically acceptable salts, hydrates, esters, or salts of such esters, as well as pharmaceutically acceptable slips that are safe and sufficient in therapeutic doses Agent so that the homogeneity of the composition can be maintained before tabletting Generally speaking, the particle sizes of these two active ingredients are not the same, and the homogeneity of the prescription refers to the main wounds, including lamivudine, chitofidine, and slip agents, which are indeed evenly dispersed in the final product. For various parts, taking film-coated tablets as an example, the active ingredients should be evenly dispersed in the core of the tablet. The composition of the present invention may also be added with a safe and sufficient therapeutic dose of a diluent and a safe and sufficient therapeutic dose of a disintegrating agent, if necessary. , And a safe and sufficient therapeutic dose of lubricant, or any of the __________ commonly used in this art-9-the size of this paper is ^ home standard ((: called 8 4 specifications ~ ^^^^ 572759 A7 V. invention Description (. Other safe and sufficient therapeutic doses of excipients, the chemical name of lamivudine (also known as 3TCtm) (2R, cis) _4_aminomethylol-1,3 · oxythiol alkane_5- Gib (1H) _pyrimidin_2_one, also known as b-)-2 ', 3f-dideoxy, 3'thiocytosine ribozyme, is a synthetic nucleoside, which has Antiviral activity. In vitro tests have shown that in the cell, lamivudine will be phosphorylated to form Active 5'-dipic acid metabolite (L-Tp), the main mode of action of L_Tp is to stop the reverse transcription by stopping the viral DNA (DNa) chain, and L-TP can also inhibit the reverse transcription Recombinant RNA (transcript virus and DNA deoxyribonucleic acid activity of transcription viruses. 2 ·, 3 · -dideoxy, 3'thiocytosine core: y: resistance to mirror image isomers The human immunodeficiency virus has the same effect, but the (_) mirror isomer (lamivudine) is less cytotoxic than the (+) mirror isomer, especially the (_) mirror isomer (lamy Anding), (-) 2,3, _dideoxy, 3, thionium nucleus is a mirror image isomer that does not contain (+), that is, about 10% w / w of (+) Mirror isomers, especially not higher than 5%, more particularly lower than about 1%. For the preparation method of lamivudine, please refer to the description of ^ 2Z2M ^ and WO95 / 29174. The printing of the pharmaceutically acceptable derivatives of the invention and lanamiphenedine by the Central Standards Bureau's Consumer Cooperatives of the Ministry of Economic Affairs refers to any drug that can provide (directly or indirectly) lamamiphenedine or its medicines. Pharmacologically acceptable salts, hydrates, esters, or salts of the vinegar, or other compounds suitable for administration to the user, of molecular groups of potent metabolites. Chitofidine chemical name is 3, -azido _3._ deoxythymidine, is a kind of pyrimidine nucleic acid, which will be converted into chitofidine trilinate by enzymes in the cell, • 10- 572759… A7: B7 V. Description of the invention (8 Chitofidine triphosphate can interfere with RNA-dependent DNA polymerase of human immunodeficiency virus (reverse transcription chest :), so it will inhibit the virus "Pharmaceutically acceptable derivative of chitofidine" means any pharmaceutically acceptable salt that can provide (directly or indirectly) chitofidine, or a molecular group of a medicinal metabolite thereof, hydrated Substances, vinegars, or salts of the esters, or other compounds suitable for use by the user, the preparation method of chitofidine can refer to the description of the appended US Patent No. 5,011,829. Sliding agents are some traditionally used to improve Granular and powdery fluids because they can reduce the friction between particles, please refer to the appendix Remington, The Science &amp; Practice of Pharmacy, 19th edition, page 1619 ( 199 5), and Lieberman, Lachman, & Schwartz, Pharmaceutical Dosage Forms: Tablets, Book I, pp. 177-178 (1989). Improving fluidity can help reduce key press clogging and malfunction, and can minimize the weight variation of the bonding agent. Sliding agents are generally added before the key is pressed. This can promote the flow of particulate matter into the ingot mold of the beater. The commonly used sliding agent is silicon dioxide (also Called colloidal seconds), fumed pulverized dioxide, fumed pulverized, light anhydrous pulverized acid, or acid anhydride. Commercially available silicon dioxide is traded under the trade names AER0SILTM and CAB0-SIL TM. Other slip agents include non-asbestos talc, silicon Sodium aluminate, calcium silicate, powdered cellulose, microcrystalline cellulose, corn starch, sodium benzoate, calcium carbonate, magnesium carbonate, metal stearates, calcium stearate, stearin-11-paper Zhang scale is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm). Please read it first. Please read the above precautions on this page before ordering the Central Standards Bureau of the Ministry of Economic Affairs.

2. Description of the invention (=, zinc stearate, st_wetc, tincture, starch test, laurel root, or magnesium dioxide. The mechanism of improving the fluidity of the sliding agent is: (1) its chemical properties and composition The relationship between the chemical properties of the other ingredients, and; (ii) = the physical properties of the activator and other ingredients of the granular or powdered composition, such as size, shape, distribution, and humidity and temperature of the composition. The discussion of the active ingredient segregation in pharmaceutical compositions, powders, and granules made the inventors unexpectedly find that the sliding agent can reduce the segregation effect of the main ingredients, so the homogeneity of the pharmaceutical composition, powders, and granules can be improved. The invention uses a sliding agent of 0.05% to about 100%. If it is less than 0.05%, the homogeneity is insufficient, and when it is more than 100%, the homogeneity does not improve more. ¾ Silicon dioxide is a preferred sliding agent because it is quite inert, and the preferred form of silicon dioxide is fume colloidal silicon dioxide, which is submicroscopic fume silicon. It is a light, non-sandy amorphous powder, and its application range is especially from about 0.05% to about 1.0% / 0.00%, because if it is less than 0.05%, the homogeneity is insufficient, and when it is higher than 1.0% There is no more improvement in the homogeneity. When using the sliding agent to improve the fluidity, it is generally added to the composition during the lubricating step before the ingot. This can be found in the appendix Remington, The Science &amp; Practice of Pharmacv ,, i 9th edition, page 1619 (1995), however, the present invention is a mixture at the beginning-12-This paper size applies Chinese National Standard (CNS) A4 specification (210X297 Gongcheng) Central Standard of the Ministry of Economic Affairs Bureau Staff Consumer Cooperatives Fanfan 572759

2. Description of the invention (1 ()) The sliding agent is added, so that the mixture can improve and maintain the homogeneity during the processing before the ingot is cast. &quot; The pharmaceutical prescription of the present invention is more preferred for oral administration. Such a prescription can be made into individual units, such as lozenges, capsules, or any other suitable for oral administration, and can be combined with the present invention. Compatible dosage forms, each dosage unit contains a predetermined amount of active ingredients, a particularly suitable prescription is a dry-pressed tablet, which can contain traditional excipients, such as adhesives, that are safe and sufficient to treat , Fillers, lubricants, or disintegrating agents, tablets can also be coated according to any method known to those skilled in this art, without affecting the release properties of the tablets or other physical or chemical properties of the present invention. Properties, the tablet and sugar-coated part, please refer to the appendix of the science and practice of Remington, iJ | The The ^

PxactLce of Pharmacy), 19th edition (1995), descriptions and legends, if necessary, the above can also be modified according to any method known to those skilled in this type of technology, so that the effective ingredients are slowly released. The prescription may also contain a safe and sufficient therapeutic dose of other active ingredients, such as antibacterial agents or preservatives. The composition of the present invention is suitable for administration to humans or other mammals, especially for oral administration. However, other medical personnel or persons specializing in pharmaceutical dosage form administration techniques, such as pharmacists, nurses, etc., also use the route of administration. It is not excluded to use. Methods such as this can be crushed in a solid dosage form, and then added to an appropriate drug delivery vehicle to make a vaccination agent for rectal administration. Other routes of administration can also include topical and inhalation. Those who are familiar with this technique will also understand that the effective ingredients of the treatment agent -13-This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) -----

572759 I A7 ---- B7 V. Description of the invention (U) The amount of 'U' will vary depending on a number of factors, including the condition during treatment, the age and condition of the patient, and the final judgment of the attending physician, veterinarian or medical staff 'However, in general, the current recommended oral dose of lamivudine for adults and adolescents is 150 mg twice daily with chitofidine and is lighter (less than 50 kg or 110 pounds). For adults, the recommended oral dose is 2 mg / kg twice daily with chitofidine. For pediatric patients from 3 months to 12 years old, the recommended oral dose is 4 mg / kg twice daily with chitofidine. . The recommended oral dose of Tongwei 'Qiduo Heding is 600 mg per day, and other antiretroviral drugs are used. For pediatric patients aged 3 months to 12 years, the recommended oral dose is 180 mg / m2 every 6 hours, or 720 per day. mg / m 'and does not exceed 200 mg every 6 hours. The composition of the present invention enables patients to have greater freedom when using multi-drug therapy, 'no longer need to remember the complicated time and procedure of taking medicine every day, because the combination of lamivudine and chitofidine In a single preparation, the required daily dose is in one preparation or a divided preparation, especially when the preparation is divided, it can be administered at appropriate intervals, for example, divided into two, three, four or more small doses per day. Drugs, especially in divided doses 2 times a day. Printed by the Central Standards Bureau, Ministry of Economic Affairs and Consumer Cooperatives ^ The composition of the present invention is formed as a unit dose preparation, which can facilitate the administration of 2 different drugs, for example, each unit dose preparation contains lamivudine from about 15 to about 1000 mg , Especially about 100 to about 500 mg of lamivudine, more specifically 150 mg of lamivudine, and about 30 to about 1000 mg of chitofidine, especially about 200 mg to about about 200 500 mg 'is more particularly 300 mg of Chitofidine. -14- This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 572759 A7 B7 V. Description of the invention (12 The composition of the present invention can be used in combination with other medical treatments, part of the practice. / 禾 刎潦 The present: The pharmaceutical composition can also be made to contain a safe and effective therapeutic amount of lamivudine, or-a pharmaceutically acceptable% of its derivative; a safe and effective therapeutic amount of chitofidine or A pharmaceutically acceptable derivative thereof: and a safe and effective therapeutic amount of a pharmaceutically acceptable slip agent. The Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs prints any kind of specialty tablets, capsules, Or other methods that are well-known to those skilled in the art of solid dosage forms for oral administration are suitable for packaging, lozenges, troches, or other solid dosage forms suitable for oral administration, as long as they do not cause degradation of the ingredients of the present invention. It can be packaged and stored in various materials, especially glass and plastic bottles, and also includes unit dose aluminum foil packaging. The packaging materials can also be printed with labels and information related to the pharmaceutical composition. In addition, the product can also contain brochures, reports, notices, instructions or leaflets with product information printed. This kind of drug information is called "imitation list" in the pharmaceutical industry. The imitation list can be attached or shot. Included in the documentation of the product, the imitation order and the labeling document of any product can provide relevant information about the pharmaceutical composition. This kind of information and labeling for medical personnel and patients' reference is to explain the composition, dosage, and other Various authorities, such as those required by the United States Food and Drug Administration. The composition of the present invention can be applied to the physical and chemical properties of the composition, and is a method commonly used by people specializing in the preparation of oral preparations by using dry pressing to make granules And technology, and prescription, please refer to the appendix Remington, The Science &amp; Practice of Pharmacy. 19th edition, 1615-1623, pages 1625-1648, and -15- this paper The standard is applicable to the Chinese National Standard (CNS) A4 specification (210X29 * 7 mm). It is 30.0.00150.00 269.63 22.50 2.25 5.63. Printed by Fei Cooperative, Description of Invention (13 Other Application Chapters (1995). From the aspect of method, the present invention ^ gives people ~ $ 甘 v, and 5 things, can be as before, ', mouth full and foot warm, , A is recognized as the king of the king and has a sufficient therapeutic dose, and this type of female punishment is large. ',, ·' will be treated due to the plastic state and size of the mammal, and the desired therapeutic effect. The following examples are for the scope of the present invention.内 I ”α &amp; can be further explained by special examples. These examples are provided for clarity only. ^ Without limiting the scope and spirit of the present invention, it does not limit any variables used. Example 1 7 ^ --- --- free complex gram) a Kidado phenidine lan Mifedidin microcellulose cellulose NF sodium starch glycolate NF colloidal silicon dioxide NF magnesium stearate Example 2 Preparation of this manufacturing step The quantity of the example is based on a typical batch of 400 kg, which can be adjusted according to the batch. First of all, the following quantities are weighed from the raw materials: -16- The size of this paper is in accordance with the Chinese National Standard (CNS) Α4 specification (2! 〇 × 297 mm)

572759 A7 B7

Qiduo Feiding Lan Mifidine Micronized Cellulose NF Dianfen Sodium Glycolate NF Colloidal Silicon Dioxide NF Magnesium Stearate The above ingredients are printed by Russell-SIV Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (14 (mg 160.00 80.00 143.80 12.00 1.20 3.00 sieve, matched with No. 14 sieve (aperture 1.4 mm)), or equivalent sieved, and placed in a stainless steel mixing container. The micronized cellulose NF, sodium starch glycolate NF and colloidal silica must first be mixed with a suitable mixer, such as Matc. Buis bm type mixer, v type mixer or grade mixer 2 For the clock, add magnesium stearate, and continue mixing for about 2 minutes. After the lubricated mixture, use a suitable rotary tableting machine to beat the ingot. Generally use Courtoy R_190, R-200 or the same grade. During the ingot process, the weight and hardness of the tablet must be controlled at appropriate intervals, and it can be adjusted if necessary. -17 This paper size applies to China National Standard (CNS) A4 (210X 297 mm) I — "MM May 7, P Shu said application of ~ 86. 11. 11. Case No. 086116822 Category Λ ^ 1κ ^ ^ each shed more than filling by the Council)

A4 C4 Chinese Manual Replacement Page (January 1992) Saimingtu — Mingyi ^ One Patent Specification-, Zero Name Chinese Medicine Composition Containing Lamiphenidine, Chitofidine and Slipping Agent English COMPOSITION C0MPRISING LAMIVUDINE, ZIDOVUDINE AND A GLIDANTn Name Nationality 1. Gerry Wayne Gerson 2. Allen Wayne Wood 3. Catherine Jenteveld 1.2.3. All of them live and live in the United States 1.2.2. · All the names of Glaxo Wellcome Co., Ltd., No. 5 Moore Road, Research Triangle Park, North Carolina, United States. (Institute) Glaxo Building, Glaxo Building, Berkeley Avenue, Greenford, Middlesex, UK Grambridden Paper Mark New Zealand Applicable Standards (CNS) M Specifications (21Gχ297 Public Love)

Claims (1)

572759 A8 B8 C8 D8 Patent Application No. 086116822 〃! Provincial Chinese Application for Patent Scope Replacement (May 1992), Patent Application Scope 1. A pharmaceutical composition containing 0 Shi Wang and an effective therapeutic amount of orchid Lamivudine or a pharmaceutically acceptable derivative thereof; 1 i) King Shi and a therapeutically effective amount of zidovudine or a pharmaceutically acceptable derivative thereof; and in) as a slip agent component The content of silicon dioxide is about 0.05 to about 10.0% by weight based on the total weight of all ingredients. 2. The pharmaceutical composition according to item 丨 of the patent application scope, which further contains another slipping agent component, which is selected from the group consisting of: sodium aluminum silicate, silicic acid powder, cellulose, microcrystalline fiber Vegetarian, corn starch, benzoate steel 'carbonate bow' magnesium carbonate, non-asbestos talc powder, metal stearic acid salt "stiffy month private transfer 'stearin, zinc stearate, stearowet C, starch, starch1 500, magnesium lauryl sulfate, or magnesium dioxide. 3. The pharmaceutical composition according to item 1 or 2 of the patent application scope, wherein the lamivudine content per unit dosage form is about 5 to about 15,000 mg. 4. For example, the pharmaceutical composition according to item 3 of the patent application, wherein the lamivudine content per unit dosage form is about 1000 to about 500 mg. 5. The pharmaceutical composition according to item 4 of the patent application, wherein each The unit dosage form has a lamivudine content of 150 mg. 6. The pharmaceutical composition according to item 1 or 2 of the patent application scope, wherein the chitofidine content per unit dosage form is about 30 to about 1,000 mg. 7. The pharmaceutical composition as claimed in claim 6 of the patent scope, wherein Muffin foot content is about 200 to about 500 mg. 8. The pharmaceutical composition of item 7 in the scope of patent application, in which the paper size per unit dosage form applies the Chinese National Standard (CNS) A4 specification (210 X 297 public love) 572759 The content of Chimufidine is 3 0 0 m g. 9. If = please claim the pharmaceutical composition of item 丨 or 2 of the patent, wherein Lamium ^ must not substantially contain the corresponding (+) mirror isomer. Non-10. The pharmaceutical composition according to item 1 of the scope of patent application, wherein the content of (+) isomers does not exceed the content of lamivudine. 11. The pharmaceutical composition according to claim 1 or 2, wherein the composition is coated with a pharmaceutically acceptable coating. Q12. The pharmaceutical composition of item i or 2 of the scope of patent application is for the treatment, reversal, alleviation or inhibition of retrovirus infection. / Q 13 · The pharmaceutical composition according to item 2 of the patent application scope, wherein the reverse green virus refers to immunodeficiency virus, including human immunodeficiency virus. Bae η m -2-