阅读说明：本技术 一种缬更昔洛韦组合物 (Valganciclovir composition ) 是由 王国军 陈波 奚忠 田胜 孙浩 李志丹 于 2019-09-19 设计创作，主要内容包括：本发明公开了一种缬更昔洛韦组合物,其原料按重量份比包括：缬更昔洛韦盐酸盐50-75份、羧甲基淀粉钠8-12份、填充剂5-8份、乳糖3-6份、番茄素15-25份、粘合剂2-5份、稳定剂3-7份,其制备方法包括以下步骤：S1、过筛,S2、粘合剂制备,S3、混料,S4、压片,本发明涉及制药技术领域。该缬更昔洛韦组合物,添加了一定量的番茄素,番茄素能够活化免疫细胞,保护吞噬细胞免受自身的氧化损伤,促进某些白介素产生及抑制炎症介质生成,具有提高人体免疫力的作用,且番茄素有助于消化,能够加强人体对摄入药品的吸收,提高有效成分的利用率,且该缬更昔洛韦组合物通过添加粘合剂和填充剂羧甲基淀粉钠,压片效果更好,不易松散,便于保存。(The invention discloses a valganciclovir composition which comprises the following raw materials in parts by weight: 50-75 parts of valganciclovir hydrochloride, 8-12 parts of sodium carboxymethyl starch, 5-8 parts of a filling agent, 3-6 parts of lactose, 15-25 parts of lycopene, 2-5 parts of an adhesive and 3-7 parts of a stabilizer, wherein the preparation method comprises the following steps: s1, sieving, S2, preparing an adhesive, S3, mixing, S4 and tabletting, and relates to the technical field of pharmacy. The valganciclovir composition is added with a certain amount of the lycopene, the lycopene can activate immune cells, protect phagocytes from self oxidative damage, promote the production of certain interleukins and inhibit the generation of inflammatory media, has the function of improving the immunity of human bodies, is helpful for digestion, can strengthen the absorption of human bodies to ingested medicines, improves the utilization rate of effective components, and has better tabletting effect, difficult loosening and convenient storage by adding the adhesive and the filler carboxymethyl starch sodium.)

1. A valganciclovir composition comprising: the raw materials comprise the following components in parts by weight: 50-75 parts of valganciclovir hydrochloride, 8-12 parts of sodium carboxymethyl starch, 5-8 parts of a filler, 3-6 parts of lactose, 15-25 parts of lycopene, 2-5 parts of an adhesive and 3-7 parts of a stabilizer.

2. The valganciclovir composition according to claim 1, wherein: the raw materials comprise the following components: 50 parts of valganciclovir hydrochloride, 8 parts of sodium carboxymethyl starch, 5 parts of a filler, 3 parts of lactose, 15 parts of lycopene, 2 parts of an adhesive and 3 parts of a stabilizer.

3. The valganciclovir composition according to claim 1, wherein: the raw materials comprise the following components: 60 parts of valganciclovir hydrochloride, 9 parts of sodium carboxymethyl starch, 6 parts of a filler, 4 parts of lactose, 18 parts of lycopene, 3 parts of an adhesive and 4 parts of a stabilizer.

4. The valganciclovir composition according to claim 1, wherein: the raw materials comprise the following components: 70 parts of valganciclovir hydrochloride, 11 parts of sodium carboxymethyl starch, 7 parts of a filler, 5 parts of lactose, 22 parts of lycopene, 4 parts of an adhesive and 6 parts of a stabilizer.

5. The valganciclovir composition according to claim 1, wherein: the raw materials comprise the following components: 75 parts of valganciclovir hydrochloride, 12 parts of sodium carboxymethyl starch, 8 parts of a filler, 6 parts of lactose, 25 parts of lycopene, 5 parts of an adhesive and 7 parts of a stabilizer.

6. A valganciclovir composition according to any one of claims 1 to 5, wherein: the filler is pregelatinized starch, the adhesive is corn starch, and the stabilizer is succinic acid.

7. A valganciclovir composition according to any one of claims 1 to 5, wherein: the preparation method specifically comprises the following steps:

s1, sieving: sieving valganciclovir hydrochloride by a sieve of 90-100 meshes, and sieving the lycopene by a sieve of 120-140 meshes;

s2, adhesive preparation: putting a proper amount of corn starch into a stirrer, adding a proper amount of cold water, stirring at a rotating speed of 600r/min to form a starch suspension, heating in a water bath at 85-95 ℃, and continuously stirring to prepare starch slurry as an adhesive for later use;

s3, mixing materials: putting a proper amount of valganciclovir hydrochloride sieved in S1 into a stirrer, adding a proper amount of stabilizer, lycopene and filler, stirring at the normal temperature at the rotating speed of 800r/min for 5-10min to uniformly mix the materials, sequentially adding a proper amount of lactose, adhesive and sodium hydroxymethyl starch, continuously stirring to obtain a material mixture, adding a wetting agent, and performing vacuum drying at the temperature of 30 ℃ by using a vacuum dryer;

s4, tabletting: and (4) pouring the mixture prepared in the step S3 into a one-step granulator for granulation, and then tabletting by using a tabletting machine.

8. The method of claim 7, wherein the valganciclovir composition is prepared by: the mixing ratio of the corn starch to the cold water in the step S2 is 1: 2.

9. The method of claim 7, wherein the valganciclovir composition is prepared by: the lubricant in step S3 is magnesium stearate and the humectant is 95% ethanol.

Technical Field

The invention relates to the technical field of pharmacy, in particular to a valganciclovir composition.

Background

Valganciclovir, a synthetic 2-deoxyguanosine analogue, is a prodrug of antiviral drug ganciclovir, can greatly reduce the toxicity of ganciclovir, has the same pharmacodynamic characteristics as ganciclovir, is rapidly hydrolyzed into ganciclovir under the action of intestinal mucosa cell esterase and liver esterase after valganciclovir is orally taken, ganciclovir generates ganciclovir triphosphate under the action of in-virus and intracellular enzyme phosphorylation, the ganciclovir is competitive with deoxyguanosine triphosphate (dGTP) as a substrate of virus DNA polymerase, so the synthesis of virus DNA is inhibited, and the activity of resisting Cytomegalovirus (CMV) is generated, in vitro, the action of ganciclovir on CMV is 26 times stronger than that of acyclovir, in vitro and in vitro studies show that ganciclovir can inhibit immune reactions caused by CMV and transplant rejection, is also effective in animal models with severe CMV infection, and a ganciclovir-resisting germ line is separated from a few patients infected by CMV, they have point mutations in the genes encoding protein kinase and viral DNA polymerase that phosphorylate ganciclovir, have a bioavailability of valganciclovir orally absorbed of 60% which is 0 times that of ganciclovir, and are rapidly absorbed and hydrolyzed to ganciclovir. The concentration of systemic valganciclovir was small for patients with CMV and HIV late stage infection and who received liver transplants because the area under the curve (AUC) values for valganciclovir 24h drug time were only 1% to 2% of ganciclovir. In patients with CMV and HIV late stage and liver transplantations, oral administration of valganciclovir 900mg 1 time a day is equivalent to an intravenous injection of 5mg/kg ganciclovir.

The valganciclovir composition is generally applied to cytomegalovirus retinitis of patients with acquired immunodeficiency syndrome, but the existing valganciclovir composition cannot achieve a good absorption effect after being ingested by the patients, the exertion of the drug effect of the valganciclovir is influenced, the utilization rate of active ingredients is reduced, and the existing valganciclovir composition has a poor tabletting effect, is easy to loosen and is not beneficial to storage.

Disclosure of Invention

Technical problem to be solved

Aiming at the defects of the prior art, the invention provides a valganciclovir composition, which solves the problems of poor absorption effect, influence on the exertion of drug effect, reduction in the utilization rate of effective components, poor tabletting effect, easiness in loosening and inconvenience in storage.

(II) technical scheme

In order to achieve the purpose, the invention is realized by the following technical scheme: a valganciclovir composition comprises the following raw materials in parts by weight: 50-75 parts of valganciclovir hydrochloride, 8-12 parts of sodium carboxymethyl starch, 5-8 parts of a filling agent, 3-6 parts of lactose, 15-25 parts of lycopene, 2-5 parts of an adhesive and 3-7 parts of a stabilizer, wherein the sodium carboxymethyl starch is also called carboxymethyl starch, is an anionic starch ether, is an electrolyte capable of being dissolved in cold water, is tasteless, nontoxic, not easy to mildew and easy to dissolve in water, is often used as a disintegrating agent of a tablet, enables the medicine to be dispersed more quickly after entering a human body, is beneficial to the absorption of the medicine by the human body, is also called lycopene, is a natural antioxidant, has a color range from yellow to red, and has high activity under a fat-soluble condition.

Preferably, the raw materials comprise the following components: 50 parts of valganciclovir hydrochloride, 8 parts of sodium carboxymethyl starch, 5 parts of a filler, 3 parts of lactose, 15 parts of lycopene, 2 parts of an adhesive and 3 parts of a stabilizer.

Preferably, the raw materials comprise the following components: 60 parts of valganciclovir hydrochloride, 9 parts of sodium carboxymethyl starch, 6 parts of a filler, 4 parts of lactose, 18 parts of lycopene, 3 parts of an adhesive and 4 parts of a stabilizer.

Preferably, the raw materials comprise the following components: 70 parts of valganciclovir hydrochloride, 11 parts of sodium carboxymethyl starch, 7 parts of a filler, 5 parts of lactose, 22 parts of lycopene, 4 parts of an adhesive and 6 parts of a stabilizer.

Preferably, the raw materials comprise the following components: 75 parts of valganciclovir hydrochloride, 12 parts of sodium carboxymethyl starch, 8 parts of a filler, 6 parts of lactose, 25 parts of lycopene, 5 parts of an adhesive and 7 parts of a stabilizer.

Preferably, the filler is pregelatinized starch, the binder is corn starch slurry, the stabilizer is succinic acid, the pregelatinized starch is modified starch, the starch is obtained by breaking part or all of starch granules by a chemical method or a mechanical method, the starch slurry (commonly called starch paste) is the most common binder in tablets, the starch slurry is mainly prepared by two methods of slurry boiling and slurry flushing, the property that the starch can be gelatinized is utilized, and the viscosity of the starch is increased sharply after gelatinization, so that the starch can be used as the binder of the tablets.

The invention also discloses a preparation method of the valganciclovir composition, which specifically comprises the following steps:

s1, sieving: sieving valganciclovir hydrochloride by a sieve of 90-100 meshes, and sieving the lycopene by a sieve of 120-140 meshes;

s2, adhesive preparation: putting a proper amount of corn starch into a stirrer, adding a proper amount of cold water, stirring at a rotating speed of 600r/min to form a starch suspension, heating in a water bath at 85-95 ℃, continuously stirring to form starch slurry serving as an adhesive for later use, wherein a direct heating mode is not adopted in the starch pasting process in order to avoid the starch slurry from being coked;

s3, mixing materials: putting a proper amount of valganciclovir hydrochloride sieved in S1 into a stirrer, adding a proper amount of stabilizer, lycopene and filler, stirring at the normal temperature at the rotating speed of 800r/min for 5-10min to uniformly mix the materials, sequentially adding a proper amount of lactose, adhesive and sodium hydroxymethyl starch, continuously stirring, simultaneously adding lubricant to prepare a material mixture, adding wetting agent, and performing vacuum drying at the temperature of 30 ℃ by using a vacuum drier;

s4, tabletting: and (4) pouring the mixture prepared in the step S3 into a one-step granulator for granulation, and then tabletting by using a tabletting machine.

Preferably, the mixing ratio of the corn starch to the cold water in the step S2 is 1: 2.

Preferably, the lubricant in step S3 is magnesium stearate, the wetting agent is 95% ethanol, and the magnesium stearate is white non-gritty fine powder; slightly smelly; it has greasy feeling when contacting with skin. The product is insoluble in water, ethanol or diethyl ether, and can be used as lubricant, antisticking agent and glidant. Is especially suitable for granulating oil and extract medicines, and the prepared granules have good fluidity and compressibility. As a glidant in direct compression. It can also be used as filter aid, clarifier and foam dripping agent, and suspending agent and thickener for liquid preparation.

(III) advantageous effects

The invention provides a valganciclovir composition. Compared with the prior art, the method has the following beneficial effects:

the valganciclovir composition comprises the following raw materials in parts by weight: 50-75 parts of valganciclovir hydrochloride, 8-12 parts of sodium carboxymethyl starch, 5-8 parts of a filling agent, 3-6 parts of lactose, 15-25 parts of lycopene, 2-5 parts of an adhesive and 3-7 parts of a stabilizer, wherein the preparation method comprises the following steps: s1, sieving: sieving valganciclovir hydrochloride by a sieve of 90-100 meshes, and sieving the lycopene by a sieve of 120-140 meshes; s2, adhesive preparation: putting a proper amount of corn starch into a stirrer, adding a proper amount of cold water, stirring at a rotating speed of 600r/min to form a starch suspension, heating in a water bath at 85-95 ℃, and continuously stirring to prepare starch slurry as an adhesive for later use; s3, mixing materials: putting a proper amount of valganciclovir hydrochloride sieved in S1 into a stirrer, adding a proper amount of stabilizer and lycopene, stirring at the normal temperature at the rotating speed of 800r/min for 5-10min to uniformly mix the materials, sequentially adding a proper amount of lactose and adhesive, continuously stirring to obtain a material mixture, adding a wetting agent, and performing vacuum drying at the temperature of 30 ℃ by using a vacuum dryer; s4, tabletting: the mixture prepared in the S3 is poured into a one-step granulator for granulation, and then tabletting is carried out by a tabletting machine, a certain amount of the lycopene is added into the valganciclovir composition, the lycopene can activate immune cells, protect phagocytes from self oxidative damage, promote T, B lymphocyte proliferation, stimulate the function of effector T cells, promote the production of certain interleukins and inhibit the generation of inflammatory mediators, so that the valganciclovir composition has the function of improving the immunity of a human body, the lycopene is helpful for digestion, can enhance the absorption of the human body to ingested medicines, and improve the utilization rate of effective components in the medicines, and the valganciclovir composition is better in tabletting effect, not easy to loosen and convenient to store by adding an adhesive and a filler, namely carboxymethyl starch sodium.

Drawings

FIG. 1 is a flow chart of the present invention;

FIG. 2 is a statistical table of comparative experimental data according to the present invention.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Referring to fig. 1-2, the embodiment of the present invention provides four technical solutions: a valganciclovir composition prepared by the process which comprises the following steps: