JPS61172831A - Anti-inflammatory, analgesic drug composition - Google Patents

Abstract

PURPOSE:A drug composition consisting of a nonsteroid anti-inflammatory analgesic, a peripheral vasodilator and a phospholipid. CONSTITUTION:A nonsteroid anti-inflammatory analgesic (e.g., phenylacetic acid type, indoleacetic acid type, indeneacetic acid type, propionic acid type, anthranilic acid type, salicylic acid type, pyrazolone type, or oxicam type; nonacidic type such as tinoridine, emorfazone, etc.) is blended with a pheripheral vasodilator (e.g., nicotinic acid, its ester, pyridine alcohol, bamethan sulfate, cyclandelate, etc.) and a phospholipid (e.g, phosphatidylcholine, hydrogented lecithin, soybean lecithin, etc.) in a ratio of 100:10-100:10-500, to give an anti-inflammatory, analgesic drug composition. It is improved absorption characteristics, especially absorption characteristics from digestive tubes, skin absorption, and extremely improved orientation to tissue cells. It is administered orally or parenterally.

Description

[Detailed Description of the Invention] [Field of Industrial Application] The present invention relates to a stable pharmaceutical composition that improves the absorption of a non-steroidal anti-inflammatory analgesic drug and further imparts tropism to tissue cells. .

[Prior art]

Nonsteroidal anti-inflammatory analgesics have strong anti-inflammatory, analgesic, and antipyretic effects, and are effective against all types of inflammation, including rheumatoid inflammation, and are also very effective in treating collagen diseases that have systemic effects. have value.

This drug can be used either orally or parenterally (dermal administration), but generally, when administered orally, it causes gastrointestinal disorders, and when administered parenterally, especially externally, it is difficult to administer. Medium trL + Cup Yu to carp 1, fight 1-11 Akane Blasphemy Turtle Fumu! -6 Rumors Therefore, the development of a highly absorbable non-steroidal anti-inflammatory analgesic drug formulation is eagerly awaited. That is, by improving absorption and by specifically delivering the drug to target tissue cells, a sufficient effect can be achieved with a small amount of administration, reducing side effects, and
Medicinal efficacy is enhanced.

[Problem that the invention seeks to solve]

An object of the present invention is to provide a pharmaceutical composition in which a non-steroidal anti-inflammatory analgesic drug has good absorption and good targeting to local cells.

[Means for solving problems]

The present inventors have conducted various studies in order to solve the above problems, and found that by combining a nonsteroidal anti-inflammatory analgesic drug and a peripheral vasodilator, and further adding phospholipid to this, a nonsteroidal anti-inflammatory drug was used. The present invention was completed based on the discovery that the absorbability of analgesics, particularly the absorbability from the gastrointestinal tract, the skin absorbability, and the directivity to tissue cells, are significantly improved.

That is, the present invention relates to non-steroidal anti-inflammatory analgesics, which are drugs that are treated as drugs and drugs.

The non-steroidal anti-inflammatory analgesic used in the present invention may be any drug as long as it has an anti-inflammatory analgesic effect. Non-steroidal anti-inflammatory analgesics are generally classified into acidic agents and non-acidic agents as described below, and of course both of them can be used in the present invention.

■Phenylacetic acid type: For example, diclofenac, alcofenac, fenbufen, etc. ■Indoleacetic acid type, indenacetic acid type, etc.: For example, Sling 7ri, indomethacin, tolmetin, etc. ■Propionic acid type: For example, ibuprofair, ketoprofen, Furupai Profen, etc. ■ Althranyl acid type: For example, flufenamisocic acid, metzenamic acid, etc. ■ Salicylic acid type: For example, aspirin, etc. ■ Pyrazolone type: For example, phenylbutacin, etc. ■ Oxycam type: For example, as a non-acidic agent such as piroxicam, , tinoridine, emorfazone, etc.

In the present invention, in addition to the acidic agents and non-acidic agents specifically shown above, salts thereof (for example, sodium salts, aluminum salts, etc.), derivatives thereof [for example, bilicyl esters, alkoxyalkyl esters, alkyl esters, etc. esters, etc.] are exemplified.

As the peripheral vasodilator used in the present invention, any peripheral vasodilator can be suitably used as long as it has a peripheral vasodilatory action (particularly, when administered to the skin, it has such an action). Specific examples of peripheral vasodilators include the following compounds: nicotinic acid and its esters (e.g., benzyl ester, β-butoxyethyl ester, nicamethate, inositol hexanicotinate, heprocanicate, nicotine acid amides, etc.), pyridine alcohols (e.g., 3-pyridine methanol, etc.), bamethane sulfate, siflanderate, etc.

As the phospholipid used in the present invention, not only the phospholipid itself but also the form of a phospholipid-containing product can be used in the present invention. Specific examples of such phospholipids include phosphatidylcholine, phosphatidylethanolamine, sphingomylin, hydrogenated lecithin, soybean lecithin, egg yolk lecithin, and the like.

The proportion of non-steroidal anti-inflammatory drugs, peripheral vasodilators and phospholipids is usually about 10-100% by weight for non-steroidal anti-inflammatory drugs, and 10-500% by weight for phospholipids. %, preferably 100~
It is blended in an amount of about 300% by weight.

The pharmaceutical composition of the present invention contains a non-steroidal anti-inflammatory analgesic drug by employing conventional formulation techniques! l! $1e
Il! ! I can do it. Such preparations may be either parenteral preparations or oral preparations. Depending on the dosage form used, the preparations may be made into powders or tablets with excipients such as cyclodextrin or lactose, or with rice oil, lauric acid, etc. This is done by emulsifying it with soybean oil, etc., or making it into a stimulant using Witepsol, polyethylene glycol, etc.

The composition of the present invention can be administered to mammals such as humans, dogs, mice, rats, and horses, and exhibits excellent analgesic and antiinflammatory effects.

The dosage varies depending on the subject, administration route, dosage form, symptoms, etc., but when administering ointment containing indomethacin (IM) externally for the purpose of treating myalgia, post-traumatic tumors, etc. in adults, Approximately 1 to 100 mg per day is administered in divided doses.

[Effect]

The composition of the present invention has a vasodilatory effect due to the effect of peripheral vasodilators and an effect of increasing skin temperature, which increases the absorption of nonsteroidal anti-inflammatory drugs. Coupled with the enhanced local concentration of the anti-inflammatory analgesic, the non-steroidal anti-inflammatory analgesic can effectively reach the local area. Therefore, the amount of the drug to be administered is reduced, adverse reactions such as gastrointestinal disorders during oral administration are reduced, and even when administered externally, sufficient effects can be achieved with a small amount of administration.

[Experiment example/Example]

Experimental Example 1 The ointment-like test preparations listed in Table 1 were administered to male Donryu rats (8 rats per group) weighing approximately 130 g, and the anti-inflammatory effects of each preparation were investigated.

As an ointment related to the present invention, one prepared according to Example 1 was used.

The hair on the back of the rat was removed, and 24 hours later, 0.1 ml of 1% carrageenan was injected into the back of the rat. Immediately after that, the test preparation
0+ag was applied, and around 25 hours later, 1% Evans Blue physiological saline was administered intravenously (0.5 ml/100 g). After 30 minutes, the animals were sacrificed by exsanguination and the back skin was peeled off. The skin of the blue-stained area was punched out, and the inhibition rate was determined from the amount of leaked pigment (Cn/5ite) and compared with an untreated control group. The results are shown in Table 1.

Table 1 Each symbol in Table 1 means the following. 2NB: Nicotinic acid benzyl ester L: Egg yolk lecithin (approximately 70% as phosphatidylcholine) ■M: Indomethacin Inteban: Manufactured by Sumitomo Chemical Co., Ltd., IM: 1% Experiment Example 2 Using the formulation of Example 1 using CCl4I instead of IM as a test drug, the absorption and excretion properties of the composition of the present invention through the skin were investigated.

Male Donryu rats (8 rats per group) were used as test animals.
Using a test drug, the test drug was applied to the front parts of the mice, and the following items were investigated.

Absorption of the drug through the skin (skin absorption rate was determined by measuring the residual amount in the skin; Figure 1) Radioactivity of C14 in the skin (Figure 2) Radioactivity of C14 in blood and plasma (Figure 3) Figure) Radioactivity of 014 in urine (Figure 4) Radioactivity of 01 in feces (Figure 5) As seen in Figures 1 to 5. Transfer to IM+L formulation, IM+N
It promotes better action than B formulation, prolongs the action time, and accelerates excretion.

Example 1 (Manufacture of gel ointment) Add Hibis Wako (10 ml) to 30 cc of purified water without stirring.
4) Mix 1.1 g. To this, add 22 cc of propylene glycol and then 5 cc'of ethyl alcohol to make it uniform.

Next, add 7C of benzyl alcohol to 1.5g of egg yolk lecithin.
C% indomethacin 0.5 g, nicotinic acid benzyl ester 0.5 g, diisopropyl adipate 1.5 g, ethyl alcohol 10.0 cc, propylene glycol 10 cc, polyethylene glycol 10. Occ is added and heated to about 50°C to completely dissolve, and then cooled to room temperature. ...(A) Liquid 1.1 g of diisopropanolamine is dissolved in 6°6 cc of water, and this is added to (^) liquid to prepare a gel.

The basic pH is 6.5.

Example 2 In the above procedure, 1.0 g of diclofenac Na salt was added instead of indomethacin to prepare a gel ointment.

Other analgesic and anti-inflammatory gel ointments are similarly manufactured.

Example 3 (Manufacture of capsules) Piroxicam 25 mg, 3-pyrisylmethanol 25
mg of 3-bilicyl methanol tartrate and 75 mg of egg yolk lecithin are dissolved and mixed in chloroform. Completely distill off the chloroform, add 40 mg of lactose,
Take 42+mg of corn starch, mix it and make 3%
Add methylcellulose paste and knead (1.2 mg of methylcellulose is added).

The mixture was granulated through a 16-mesh sieve and heated to 50°C.
Dry with.

After drying, the mixture is sized through a 24-mesh sieve, and 1 mg of magnesium stearate is added and mixed to obtain granules. This is filled into 150-g capsules to produce capsules.

(Left below) Example 4 (Production of poultice) Purified water was added to the above composition to make 100 g to produce a poultice.

〔effect〕

According to the composition of the present invention, compared to a nonsteroidal anti-inflammatory drug alone, a combination of a nonsteroidal anti-inflammatory drug and a peripheral vasodilator, and a combination of a nonsteroidal anti-inflammatory drug and a phospholipid, Since the absorption of anti-inflammatory and analgesic drugs is significantly increased, they exhibit remarkable anti-inflammatory and analgesic effects even when administered in small doses, have few adverse reactions, and are extremely useful therapeutically.

[Brief explanation of drawings]

1 to 5 are graphs showing the effects of the pharmaceutical composition of the present invention. Patent applicant Satoshi Nakanishi □□■ Figure 1 Time (hr,) Figure 2 ft1l! 1 (hr,) Figure 3 4 hours (hr,) Figure 4 Time rhr,) Figure 5 Time (hr,) Procedural amendment stamp button July 5, 1985

Claims (1)

[Claims] A pharmaceutical composition comprising a nonsteroidal anti-inflammatory drug, a peripheral vasodilator, and a phospholipid.