CN107198682A - A kind of refrigerant anesthetic and its application - Google Patents
A kind of refrigerant anesthetic and its application Download PDFInfo
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- CN107198682A CN107198682A CN201610154061.2A CN201610154061A CN107198682A CN 107198682 A CN107198682 A CN 107198682A CN 201610154061 A CN201610154061 A CN 201610154061A CN 107198682 A CN107198682 A CN 107198682A
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- 239000003507 refrigerant Substances 0.000 title abstract description 8
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- 239000007921 spray Substances 0.000 claims abstract description 20
- 239000003595 mist Substances 0.000 claims abstract description 8
- 206010052428 Wound Diseases 0.000 claims abstract description 6
- 210000004400 mucous membrane Anatomy 0.000 claims abstract description 5
- CDOOAUSHHFGWSA-OWOJBTEDSA-N (e)-1,3,3,3-tetrafluoroprop-1-ene Chemical compound F\C=C\C(F)(F)F CDOOAUSHHFGWSA-OWOJBTEDSA-N 0.000 claims description 13
- 206010002091 Anaesthesia Diseases 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
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- FDOPVENYMZRARC-UHFFFAOYSA-N 1,1,1,2,2-pentafluoropropane Chemical class CC(F)(F)C(F)(F)F FDOPVENYMZRARC-UHFFFAOYSA-N 0.000 abstract 1
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- 238000000034 method Methods 0.000 description 8
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- MSSNHSVIGIHOJA-UHFFFAOYSA-N pentafluoropropane Chemical compound FC(F)CC(F)(F)F MSSNHSVIGIHOJA-UHFFFAOYSA-N 0.000 description 5
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- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
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- 238000011156 evaluation Methods 0.000 description 3
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
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- 206010006811 Bursitis Diseases 0.000 description 2
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- 241000700159 Rattus Species 0.000 description 2
- 206010044074 Torticollis Diseases 0.000 description 2
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- LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical group FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 1
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- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
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- 206010041738 Sports injury Diseases 0.000 description 1
- 206010042674 Swelling Diseases 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 238000005299 abrasion Methods 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
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- 238000001949 anaesthesia Methods 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 229940035674 anesthetics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
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- 208000034526 bruise Diseases 0.000 description 1
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- 230000001066 destructive effect Effects 0.000 description 1
- 229960000385 dyclonine Drugs 0.000 description 1
- BZEWSEKUUPWQDQ-UHFFFAOYSA-N dyclonine Chemical compound C1=CC(OCCCC)=CC=C1C(=O)CCN1CCCCC1 BZEWSEKUUPWQDQ-UHFFFAOYSA-N 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
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- 208000013465 muscle pain Diseases 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 230000007830 nerve conduction Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000008058 pain sensation Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000002984 plastic foam Substances 0.000 description 1
- 229920000582 polyisocyanurate Polymers 0.000 description 1
- 239000011495 polyisocyanurate Substances 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000009958 sewing Methods 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 208000026843 stiff neck Diseases 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000002937 thermal insulation foam Substances 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 210000001170 unmyelinated nerve fiber Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/02—Halogenated hydrocarbons
- A61K31/035—Halogenated hydrocarbons having aliphatic unsaturation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/02—Halogenated hydrocarbons
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses a kind of refrigerant anesthetic and its application, the refrigerant anesthetic is by 1,1,13, and 3 pentafluoropropanes and the trans propylene of 1,3,3,3 tetrafluoro 1 are constituted.Present invention can apply to the crymoanesthesia medically to tissues such as skin, mucous membranes.Mist type or jet flow type spray can be made in the present invention, be locally applied to skin, complete mucous membrane and open small wound, injection, pain caused by minor operation can effectively be controlled, also can the effectively small injury gained in sports of temporary relief, such as sprain, dampen, hurting, abrading the pain of situation.Wherein, jet flow type spray can also be used for the auxiliary treatment of myofacial pain, limitation of movement and muscular tone.
Description
Technical Field
The invention relates to a freezing anesthetic and application of the freezing anesthetic in refrigeration anesthesia of skin, mucosa and surfaces of small open wounds.
Background
In medical clinic, local anesthetics can reversibly block the occurrence and transmission of sensory nerve impulses locally during administration, and generally, the effect of the local anesthetics is limited to the administration site and rapidly disappears as the drugs diffuse from the administration site. The common local anesthetic drugs such as procaine and lidocaine can be widely used for infiltration anesthesia and nerve block induction, and have the defects that high concentration is required during use, so that the risks of tissue stimulation and tissue damage are increased, and side effects are large. For some situations, topical local anesthetics are more beneficial than injection anesthetics to improve safety and convenience of use. At present, most of the bases of the skin anesthetic for external use are emulsions, creams or gels containing ethanol solution, such as local anesthetic 5% Enra (EMLA) cream, lidocaine ointment, dyclonine cream, fat-soluble dicaine, etc., which are popular at present. To further reduce the risk, liquid nitrogen cryo-anesthesia treatments were invented, as well as a cryo-anesthetic comprising tetrafluoroethane, oil-bearing oils and ethanol. Based on the excellent clinical characteristics of the cold anesthetic, more new products with new formula are emerging continuously.
Trans-1, 3,3, 3-tetrafluoro-1-propene with the formula C3H2F4Trans HFO-1234ze, which is usually a gas at normal temperature and pressure, usually a high-pressure gas, liquefied gas. In industry, the compound has a very large number of applications, such as refrigerants, foaming agents, cleaning agents, pesticide aids and the like, and can also be used as a component of a medical disinfectant. There is still little research effort, especially in the clinical field, for further use of this compound, especially for potential clinical applications. The present inventors have continued research and study and need to utilize the freezing property of the compound to apply it to a cryoanesthetic.
Disclosure of Invention
The invention aims to provide a cryo-anesthetic and to apply the cryo-anesthetic in the medical field for obtaining local cryo-anesthesia of skin, mucous membranes and small open wounds.
The solution provided by the invention is as follows:
a freezing anesthetic comprises the following components in percentage by weight:
85-97% of 1,1,1-3, 3-pentafluoropropane,
3-15% of trans-1, 3,3, 3-tetrafluoro-1-propene.
Wherein, the preferable formula is as follows:
90-95% of 1,1,1-3, 3-pentafluoropropane,
5-10% trans-1, 3,3, 3-tetrafluoro-1-propene.
According to the administration form and the requirement of the product, a proper amount of medical auxiliary materials commonly used by those skilled in the art, such as ethanol and other auxiliary materials, can be added into the cryoanesthetic provided by the invention, which is not limited in any way. The preferred cryoanesthetic comprises the following components in percentage by weight:
85-97% of 1,1,1-3, 3-pentafluoropropane,
3-15% trans-1, 3,3, 3-tetrafluoro-1-propene, and
appropriate amount of auxiliary materials.
Further, the above-mentioned cryoanesthetic is applied medically in the form of a spray for administration by spraying, wherein the spray may be of a mist type or a jet type.
The above-mentioned 1,1,1-3, 3-pentafluoropropane, of the formula: CF (compact flash)3CH2CHF2Chemical abstracts number (CAS No.): 460-73-1, HFC-245fa for short. Under normal pressure, the liquid is colorless liquid at 15 ℃, the saturated vapor pressure (20 ℃) is 122.7KPa, the liquid density (20 ℃) is 1.32g/ml, the liquid is colorless gas at 20 ℃, and the solubility in water (PH is 8.11-8.62 room temperature) is 7180 mg/L. Currently, HFC-245fa is mainly used in blowing agents such as rigid polyurethane and polyisocyanurate foams, insulating plastic foams, insulation foams and the like.
In the industrial field, HFC-245fa can be used as a refrigerant alone or can be used as a refrigerant by being matched with other components. In the present invention, HFC-245fa is used as the main source of spray power for the spray at the liquefaction temperature.
The trans-1, 3,3, 3-tetrafluoro-1-propene is non-toxic, non-flammable, non-destructive to the ozone layer, short in retention time in the atmosphere, little in influence on the environment, stable in chemical properties, and has obvious advantages compared with other refrigerants. The invention applies trans-1, 3,3, 3-tetrafluoro-1-propene to the cryoanesthesia in the medical field in a breakthrough way. The cooling can play the role of an anesthetic, namely, the trans-1, 3,3, 3-tetrafluoro-1-propylene can be quickly evaporated on the surface of the tissue so as to reduce the temperature of the tissue area, and the effect can be continued for a certain time to generate the anesthetic effect. A large amount of experimental and clinical data show that the cryoanesthetic can be applied to the surface cryoanesthesia of skin, mucosa and small open wounds in medicine, has a good anesthetic effect and has excellent safety.
The 1,1,1-3, 3-pentafluoropropane contained in the product of the present invention can be used as a jet power source of an aerosol, and simultaneously produces a synergistic effect with trans-1, 3,3, 3-tetrafluoro-1-propene, and the mixture thereof forms a low evaporation rate, is dispersed to the skin surface through a special release system and immediately evaporates, forms an instant cooling effect, and slows down the nerve conduction speed of C-fibers and a-fibers constituting the peripheral nervous system, thereby blocking the input of pain to the spinal cord.
The freezing spray (skin refrigerant) provided by the invention can be locally applied to skin, intact mucous membranes (such as oral cavity, nasal cavity channels, lips and the like) and small open wounds. Both the mist type and the jet type are used for controlling pain caused by injection (such as venipuncture, intravenous injection, cosmetic surgery, etc.) and minor surgery (such as removal of furuncle, pus discharge, needle sewing, etc.), and can temporarily relieve pain caused by minor sports injury, such as sprain, contusion, cut, bruise, etc. Preferably, the present invention, when used with a jet-type cryogenic spray, can also be used as an adjunct treatment against irritations such as myofascial pain, restricted movement and muscle tone.
Detailed Description
The present invention is described in detail by the following examples.
The 1,1,1-3, 3-pentafluoropropane and trans-1, 3,3, 3-tetrafluoro-1-propene used in the examples of the present invention all meet medically acceptable standards and are commercially available in the market. During production, the two raw materials are mixed in proportion, then enter a container through a valve, are filled under pressure, and then are sealed and are detected to be leaked. As the spray agent to be used in medicine, either a jet type or a mist type, those skilled in the art can produce it by a well-known method, and the present invention is not limited thereto.
The specific formula composition is shown in the following table:
| 1,1,1-3, 3-pentafluoropropane | Trans-1, 3,3, 3-tetrafluoro-1-propene | |
| Example 1 | 850g | 150g |
| Example 2 | 900g | 100g |
| Example 3 | 930g | 70g |
| Example 4 | 950g | 50g |
The using method comprises the following steps:
the obtained mist type cryoanesthesia spraying agent can be used for holding the tank body by hands, and forcibly pressing a brake button at a distance of 5-20 cm from a treatment position to spray a product from the tank. The specific application method is as follows according to different clinical conditions:
1. anesthesia before injection
The treatment area is wiped with disinfectant and sprayed from a distance of 5-20 cm from the treatment area for about 4-10 seconds. When the skin is tight, the needle is quickly inserted. The operation may be repeated again as necessary. Other types of injections may be used in this procedure, such as intravenous injections, venipuncture, and the like.
2. Local anesthesia in minor surgery: the area of treatment was wiped with disinfectant, the adjacent area was protected with petrolatum and sprayed from a distance of 5-20 cm from the area of treatment for approximately 4-10 seconds. The anesthetic effect of rapid incision, pain relief lasts from a few seconds to 1 minute and can be repeated as needed.
3. For pain relief use, the spray can is held by hand with the can upright and sprayed from a distance of 30 to 46cm so that the fluid can meet the skin requirements to reduce the impact of fluid impact. A direct spray of 1.5 to 2cm is scanned in parallel at a speed of about 10cm per second until the entire muscle is covered, the number of scans being determined by the area of the muscle, the muscle being stretched by the spray and the intensity of successive scans being gradually increased. As the muscles relax, the relaxation of the muscles is smoothly achieved by forming a new stretched length, and the contact point can be completely disabled when the muscles reach the completely normal length, so that the pain can be relieved and the vitality can be restored. This process is repeated if necessary. Moist heat was maintained for 10 to 15 minutes after treatment, excluding any factors that generated a trigger mechanism.
Evaluation of anesthetic Properties
a. Animal(s) production
Male and female rats, meeting the pharmaceutical clinical laboratory criteria, were used, weighing between 200g and 300 g.
b. Local cryoanesthesia
The following experiments were divided into experimental and control groups. The products obtained in the above examples correspond to a set of experiments in sequence, wherein the anaesthesia part of the rat is the abdomen and the spray is in the form of mist. 3 doses were administered to each animal, 2 animals were used for each test, and the values listed in the table below are mean values. To evaluate the anesthetic effect, mechanical stimulation (in the table "needle stick") was performed at each application point with a pointed forceps, and when local contraction of the skin was observed after the mechanical stimulation, the site was considered to be not anesthetized, i.e., the pain sensation was significant. The time evaluated was 60 seconds (min).
The experiments show that the invention has local anesthesia effect on the surface of animal skin, and the anesthesia time is not less than 30 seconds under effective dose.
Second, evaluation of muscle pain-relieving Properties
a. Clinical cases
To evaluate the treatment of the present invention for conditions in which myofascial pain, limitation of movement and muscle tone are the main symptoms, the present invention has undergone a number of clinical observations before applying for a patent.
The patients between 25-55 years of age were selected, with unlimited nature, and 30 cases were selected, and clinical observations showed that the following evaluation results were obtained, including 5 cases with lumbago (due to muscle tension) clinically, 5 cases with ankle sprain clinically, 5 cases with acute stiff neck clinically, 5 cases with torticollis clinically, 5 cases with muscle cramp pain caused by trigger point, and 5 cases with acute shoulder bursitis clinically.
b. Method of treatment
Using the jet-type cryo-anesthetic spray obtained above, the canister can be held by hand and the actuator button pressed hard 5-20 cm away from the treatment site to allow the product to be ejected from the canister for approximately 4-10 seconds and avoid being ejected outside the treatment area until the skin begins to whiten. Use as needed, taking care not to freeze the skin/area.
c. Criteria for efficacy assessment
And (3) curing: the signs of symptoms completely disappeared.
The method has the following advantages: the signs of symptoms were reduced earlier.
And (4) invalidation: there was no improvement in the signs of symptoms.
d. Therapeutic results
0 case is cured clinically, accounting for 0 percent; the effective rate is 100% in 30 cases and 0 cases. All patients had some relief from the associated pain symptoms.
Through clinical observation, the jet spray product can be used as an anti-irritant to control myofascial pain, restricted movement and muscular tension pain. The jet-type analgesics can be used clinically to manifest as lumbago (due to muscle tension), acute neck stiffness, torticollis, acute shoulder bursitis, tight hamstrings, ankle sprains, and pain associated with tight muscles caused by trigger points. Pain relief promotes mobilization and recovery of early muscle function.
Clinical observations have shown that either the mist or jet-type of cryogenic spray of the present invention can be used as an adjunct therapy to temporarily relieve pain from minor athletic injuries, including pain caused by bruising, contusions, swellings, minor sprains, cuts and abrasions. The degree of cooling depends on the dosage, which is related to the length of the spray, which is sufficient for alleviating general pain. The method used is that the anesthetic effect of pain relief can last from a few seconds to 1 minute from a jet 5-20 cm from the treatment area, which can be repeated as needed.
The invention is not limited to the embodiments discussed above. The foregoing description of the specific embodiments is intended to explain and illustrate the principles involved. The embodiments described above are provided to disclose the best mode for carrying out the invention, so that those skilled in the art can apply the embodiments of the invention and various alternatives to achieve the object of the invention. Obvious modifications or alterations based on the teachings of the present invention should also be considered as falling within the scope of the present invention.
Claims (6)
1. A cold anesthetic is characterized by comprising the following components in percentage by weight:
85-97% of 1,1,1-3, 3-pentafluoropropane,
3-15% trans-1, 3,3, 3-tetrafluoro-1-propene;
or,
85-97% of 1,1,1-3, 3-pentafluoropropane,
3-15% trans-1, 3,3, 3-tetrafluoro-1-propene, and
appropriate amount of auxiliary materials.
2. A cryoanesthetic according to claim 1, characterized in that said composition is:
90-95% of 1,1,1-3, 3-pentafluoropropane,
5-10% trans-1, 3,3, 3-tetrafluoro-1-propene.
3. A cryo-anesthetic according to claim 1 or 2, characterized in that said cryo-anesthetic is applied medically in the form of a spray for administration by spraying.
4. A cryo-anesthetic agent according to claim 3, characterized in that said spray of cryo-anesthetic agent may be of the mist type or of the jet type.
5. A cryoanesthetic according to claim 1, characterized in that the main component of the adjuvant is ethanol.
6. A cryo-anesthetic according to any of claims 1-5, for use in medical superficial cryo-anesthesia of skin, mucous membranes and small open wounds, and for the adjuvant treatment of myofascial pain, exercise limitation and muscle tension.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610154061.2A CN107198682A (en) | 2016-03-17 | 2016-03-17 | A kind of refrigerant anesthetic and its application |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610154061.2A CN107198682A (en) | 2016-03-17 | 2016-03-17 | A kind of refrigerant anesthetic and its application |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107198682A true CN107198682A (en) | 2017-09-26 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113712921A (en) * | 2021-09-02 | 2021-11-30 | 沈阳德隆医疗器械有限公司 | Novel rapid local pain-relieving hemostatic and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6235265B1 (en) * | 1998-10-28 | 2001-05-22 | Alliedsignal Inc. | Evaporative coolant for topical anesthesia comprising hydrofluorocarbons and/or hydrochlorofluorocarbons |
| US6737041B1 (en) * | 1993-08-20 | 2004-05-18 | University Of Cincinnati | Non-ozone depleting vapocoolants |
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2016
- 2016-03-17 CN CN201610154061.2A patent/CN107198682A/en active Pending
Patent Citations (2)
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| US6737041B1 (en) * | 1993-08-20 | 2004-05-18 | University Of Cincinnati | Non-ozone depleting vapocoolants |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113712921A (en) * | 2021-09-02 | 2021-11-30 | 沈阳德隆医疗器械有限公司 | Novel rapid local pain-relieving hemostatic and application thereof |
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