JPH0232013A - Nasal drop - Google Patents

Abstract

PURPOSE:To a nasal drop containing hyaluronic acid and active drug, having pH in specific range, remarkably improved in efficiency of the drug by sustained release action and simultaneously capable of providing protecting effect to mucosa of nasal cavity. CONSTITUTION:The aimed nasal drop containing 0.01-2wt.%, preferably 0.05-0.5wt.% hyaluronic acid having >=10000 molecular weight and active drug capable of passing through mucosa of nasal cavity and having pH in the range of 6-8.5. Release of the drug in nasal cavity is controlled to provide sustained release effect, because the drug exists in a state included in a molecular matrix of hyaluronic acid. Further, mucosa of nasal cavity is protected by moisture retaining action and foreign matter preventing action of hyaluronic acid.

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to a novel nasal spray, and more particularly to a nasal spray containing hyaluronic acid and an active agent.

<Prior art and problems to be solved> Recently, various therapeutic methods have been developed that take advantage of the high drug absorption of the nasal mucosa and administer active drugs in the form of nasal drops. Nasal drops in the form of ointment are not easy to apply to the nasal mucosa located deep in the nasal cavity, so a spray that is inhaled into the nose in the form of a mist is popular because it delivers the necessary and sufficient amount of drug and is comfortable to use. However, since the sprays conventionally used are aqueous solutions with almost no viscosity, such as distilled water, raw saline, and aqueous phosphoric acid solutions, when administered intranasally, they do not affect anyone. In order to solve this problem, a nasal spray containing a carboxyvinyl polymer and having viscosity was developed (Japanese Patent Laid-Open No. 101318/1983).
However, since carboxyvinyl polymer is a synthetic polymer, there were still issues in terms of safety.

Means for Solving the Problems〉 The present inventors have conducted intensive research to obtain a nasal spray that does not have such problems, and as a result, they have developed a nasal spray that contains hyaluronic acid and an active agent and has a PF'16 to 8.5. The present inventors have discovered a nasal spray that has certain characteristics and have completed the present invention.

The nasal spray of the present invention is produced, for example, by adding an active agent to an aqueous solution of hyaluronic acid, and then adjusting the pH to 6 to 8.5 with an inorganic base.

The hyaluronic acid used in the present invention is an extract from a cock's comb, crystalline lens, umbilical cord, etc.
It can be used regardless of the origin, such as those derived from cultures of hyaluronic acid-producing bacteria of the genus Bococcus. Hyaluronic acid is originally synthesized in the bodies of all animals, including humans, and is a biological substance that performs important functions in each part of the body, and is used as a medicine in the fields of eye surgery and orthopedics. It is a type of mucopolysaccharide that is relatively safe.

In addition, synthetic polymers such as carboxyvinyl polymers have low degradability and may remain in the nasal cavity for a long period of time, causing negative effects, but hyaluronic acid is biodegradable and decomposes in a relatively short period of time, reducing its molecular weight. be done.

The amount of hyaluronic acid to be used is not fixed because it is closely related to the viscosity and fluidity of the nasal spray and the molecular weight of hyaluronic acid, but it ranges from 0.01 to 21, preferably 0.05.
It is used in a range of 0.5% by weight. 0.011% by weight
If the temperature is too high, the gist of the present invention will not be fully realized due to high fluidity;
If it exceeds % by weight, the fluidity will be low, making it difficult to spray and may block the nasal passages, causing discomfort. Furthermore, hyaluronic acid is said to have a very strong moisturizing effect and an effect of inhibiting the invasion of foreign substances such as viruses, and cosmetics containing hyaluronic acid that take advantage of this effect are also on sale. Similarly, the hyaluronic acid in nasal sprays not only retains water on the nasal mucosa for a long time and keeps it moist, but also prevents external microorganisms, viruses, pollen, dust, mites, etc. from coming into contact with the nasal mucosa. It also has the effect of preventing.

Furthermore, since the drug exists in a state entrapped in the molecular matrix of hyaluronic acid, drug release within the nasal cavity is controlled, resulting in a sustained release effect. Although there is no particular restriction on the molecular weight of hyaluronic acid, a molecular weight of 10,000 or more is preferred in order to fully exhibit the effects of the present invention.

Hyaluronic acid may be in the form of an acid or a salt neutralized with an inorganic base, and is ultimately used in the form of a nasal spray adjusted to pH 6 to 8.5.

As the inorganic base, hydric soda, hydric potassium, ammonia, etc. can be suitably used, and a Pl'' of less than 16 and a pH of more than 8.5 irritates the nasal mucosa.

A wide variety of active agents can be used in the preparation of the present invention, as long as they can pass through the nasal mucosa, such as antibiotics such as erythromycin, tetracycline, cephalexin, and amoxicillin, and hypnotics such as phenobarbital, etinamate, nitrazepam, and amobarbital.・Analgesics, aspirin, ibuprofen, tialamilad hydrochloride, antipyretic analgesics such as indomethacin, digoxin, digitoki'
Cardiac inotropes such as Cyn, dopamine hydrochloride, ubidecarenone, allergy agents such as diphenhydramine hydrochloride, homochlorcifrizine hydrochloride, remasten fumarate, sodium cromoglycate, gindolol, propranolol hydrochloride,
Antiarrhythmic drugs such as shisogilamide and ajmaline, tetyl hydrochloride I
Local vasoconstrictors such as Jzolin, oxymetazoline hydrochloride, naphazoline nitrate, zoltiazem hydrochloride, nifedipine,
Coronary vasodilators such as inrubito nitrate, dexamethacin,
Examples include adrenal hormones such as prednisolone acetate and triamcinolone acetonitate, and hormones such as testosterone enanthate, globsterone, and estradiol valerate.

<Example> The present invention will be explained in more detail with reference to Examples below.

Concentrations are by weight unless otherwise specified.

Example 1 Diphenhydramine hydrochloride was added to a 0.2% physiological saline solution of sodium hyaluronic acid (manufactured by Qzaichi Co., Ltd., cockscomb extract, molecular weight 800,000) under stirring to a concentration of 0.4 parts.
- was adjusted to 7 with 1% sodium hydroxide solution to obtain diphenhydramine hydrochloride nasal drops.

Example 2 Hyaluronic acid (manufactured by Denki Kagaku Kogyo Co., Ltd., cultured bacteria, molecular weight 15
Anzecillin sodium was added to a 0.07% aqueous solution of phosphorous-brewed primary potassium (0.05 molar concentration) with stirring to a concentration of 2%, and the - was adjusted to 8 with a 1% sodium hydroxide solution. Ampicillin nasal spray was obtained.

<Effects of the Invention> The nasal spray for 9tI# produced according to the present invention has the following characteristics as compared to conventional ones.

(1) Highly safe and biodegradable, so no residue remains.

(2) The drug is retained by hyaluronic acid, and its sustained release effect significantly improves drug efficiency.

(3) Hyaluronic acid's moisturizing and foreign body blocking effects protect the nasal mucosa.

Claims (1)

[Claims] Contains hyaluronic acid and active agents, pH 6-8.5
A nasal spray agent characterized by: