阅读说明：本技术 一种舌下用药物组合物 (Sublingual pharmaceutical composition ) 是由 王磊 姚胜男 陈荣 于 2018-07-10 设计创作，主要内容包括：本发明公开了一种舌下给药制剂及其制备方法,其中舌下给药制剂活性成分为依达拉奉和(+)2-莰醇,非活性成分包括赋形剂、填充剂、粘合剂、崩解剂、润滑剂、助流剂、包衣材料等。舌下给药制剂,可以避免肝脏首过效应,样品稳定性好、便于运输、使用方便等优点。(The invention discloses a sublingual administration preparation and a preparation method thereof, wherein the active ingredients of the sublingual administration preparation are edaravone and (+) 2-borneol, and the inactive ingredients comprise excipient, filler, adhesive, disintegrant, lubricant, glidant, coating material and the like. The sublingual administration preparation can avoid liver first pass effect, and has the advantages of good sample stability, convenient transportation, convenient use and the like.)

1. A sublingual tablet containing a composition of edaravone and (+) -2-borneol is characterized by containing active ingredients of edaravone or a salt thereof and (+) -2-borneol and pharmaceutically acceptable auxiliary materials, wherein the pharmaceutically acceptable auxiliary materials comprise an excipient, a filling agent, a bonding agent, a disintegrating agent, a lubricant, a glidant, a coating material and the like.

2. The pharmaceutical composition of claim 1, wherein the weight ratio of edaravone to (+) -2-borneol on a free base basis is from 4:1 to 1: 1.

3. The pharmaceutical composition of claim 1, wherein the weight ratio of edaravone to (+) -2-borneol on a free base basis is 4: 1.

4. The pharmaceutical composition of claim 1, wherein the excipient is one or more of mannitol, lactose, dextran, cysteine, glycine, and cyclodextrin.

5. The pharmaceutical composition of claim 1, wherein the filler is lactose, starch, sucrose, mannitol, sorbitol, microcrystalline cellulose, calcium dihydrogen phosphate, or the like.

6. The pharmaceutical composition of claim 1, wherein the binder is sodium carboxymethylcellulose, hypromellose, hydroxypropyl cellulose, povidone, starch, ethyl cellulose, methyl cellulose, or the like.

7. The pharmaceutical composition of claim 1, wherein the disintegrant is sodium carboxymethyl starch, hydroxypropyl cellulose, croscarmellose sodium, crospovidone, starch, or the like.

8. The process for the preparation of a pharmaceutical composition according to any one of claims 1 to 7, comprising the steps of: mixing edaravone with (+) -2-camphanol, excipient, filler, binder, disintegrant, lubricant and glidant, and tabletting.

9. A process for the preparation of a pharmaceutical composition according to any one of claims 1 to 7, comprising the steps of: mixing the edaravone with (+) -2-borneol, an excipient, a filler and an adhesive, granulating, adding a disintegrant, a lubricant and a glidant, uniformly mixing, and tabletting.

10. The sublingual tablet according to the present invention as claimed in claims 1 to 9, for use in the preparation of a medicament for the treatment of cerebrovascular diseases.

Technical Field

The invention belongs to the technical field of medicines, and relates to a sublingual pharmaceutical composition and a preparation method thereof.

Background

Edaravone (chemical name: 3-methyl-1-phenyl-2-pyrazolin-5-one) is marketed cerebral nerve protective agent: (Yakugaku Zasshi. 2004, 124(3): 99-111). Research shows that edaravone has antioxidant activity, can obviously improve the nerve defect symptoms of cerebral ischemia reperfusion animals, reduce the infarct size, reduce the degree of brain injury, relieve cerebral edema and inhibit lipid peroxidation of damaged brain tissues.

Edaravone

(formula C)₁₀H₁₀N₂O, molecular weight 174.20)

(+) -2-borneol is the main ingredient of a common traditional Chinese medicine, namely natural borneol, and the borneol has the effects of resuscitation by resuscitation, curtain by fragrance and ascending by guiding drugs, and is often used as a guiding drug to improve the treatment effect of other drugs; ben Cao Yan Yi (the Yan Yi of materia Medica) points out that borneol is weak in one way and active in adjuvant therapy. Animal experiments and in vitro experiments show that: borneol has the function of promoting the medicine to penetrate blood brain barrier.

Camphol alcohol

(formula C)₁₀H₁₈O; molecular weight 154.25)

The invention patent (CN 101848711A) entitled "a pharmaceutical composition and application thereof in preparing medicaments for treating cerebrovascular diseases" discloses application of a composition of edaravone and (+) -2-borneol injection in a specific proportion in preparing medicaments for treating cerebrovascular diseases, in particular to medicaments for treating ischemic cerebrovascular diseases.

Some acute diseases need to be relieved quickly, generally, intramuscular injection or intravenous administration is the first choice method for emergency treatment, but intramuscular injection or intravenous injection can cause pain and stimulation at the injection site, operation of medical staff is needed, and injection products and the like are needed, so that the application is limited by certain medical treatment, and the method is not suitable for patients suffering from diseases outside hospitals. The sublingual preparation is directly absorbed by sublingual mucosa, the sublingual mucosa has large surface area and strong permeability, a large number of capillaries below the mucosa are gathered to internal jugular veins and directly enter blood circulation through superior vena cava, the medicine is quickly absorbed after administration, the onset is quick, the quantification is accurate, the use is convenient, and the first pass effect of oral medicine is avoided. Compared with injections, the sublingual tablet greatly improves the convenience of medication and the compliance of clinical patients.

Disclosure of Invention

The invention aims to provide a sublingual pharmaceutical composition which comprises edaravone or a salt thereof and (+) -2-borneol. The sublingual tablet has to be released quickly to reach a certain blood concentration so as to exert the treatment effect. The invention provides a sublingual pharmaceutical composition, and main medicaments can be quickly released and absorbed under the tongue.

In order to achieve the purpose, the invention adopts the following technical scheme:

the sublingual tablet containing the composition of edaravone and (+) -2-borneol is characterized by containing active ingredients of edaravone or a salt thereof and (+) -2-borneol and pharmaceutically acceptable auxiliary materials, wherein the pharmaceutically acceptable auxiliary materials comprise an excipient, the excipient is one or more selected from mannitol, lactose, dextran, cysteine, glycine and cyclodextrin, and the preferred excipient is mannitol.

In the sublingual composition, the weight ratio of edaravone to (+) -2-borneol in terms of free base is 4:1 to 1:1, preferably, the weight ratio of edaravone to (+) -2-borneol in terms of free base is 2:1 to 1:1, and more preferably, the weight ratio of edaravone to (+) -2-borneol in terms of free base is 4: 1.

In the sublingual composition, the filler is selected from lactose, starch, sucrose, mannitol, sorbitol, microcrystalline cellulose, calcium dihydrogen phosphate, etc.

In the sublingual administration composition, the adhesive is selected from sodium carboxymethylcellulose, hypromellose, hydroxypropyl cellulose, povidone, starch, ethyl cellulose, methyl cellulose and the like.

In the sublingual administration composition, the disintegrating agent is selected from sodium carboxymethyl starch, hydroxypropyl cellulose, croscarmellose sodium, crospovidone, starch and the like.

The preparation method of the sublingual administration composition comprises the following steps: mixing edaravone with (+) -2-camphanol, excipient, filler, binder, disintegrant, lubricant and glidant, and tabletting.

The preparation method of the sublingual administration composition comprises the following steps: mixing the edaravone with (+) -2-borneol, an excipient, a filler and an adhesive, granulating, adding a disintegrant, a lubricant and a glidant, uniformly mixing, and tabletting.

The sublingual composition can be used for treating cerebrovascular diseases.

Drawings

Figure 1 examples 1 to 5 dissolution profiles.

Detailed Description

The invention discloses a sublingual administration preparation of edaravone and (+) -2-borneol, which can be realized by a person skilled in the art by properly improving process parameters or prescription ratio by taking the contents of the invention as reference and combining the principle of pharmacy. It is expressly intended that all such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the scope of the invention. While the invention has been described in terms of preferred embodiments, it will be apparent to those skilled in the art that the techniques of the invention can be implemented and practiced with modification, or with appropriate modification, and combinations of the methods and applications described herein without departing from the spirit, scope, and spirit of the invention.